Ivermectin - the anticancer potential of the antiparasitic drug

Homepage


Store


Contact

Description of the potential effects of the substance Ivermectin based on the literature. (This is not a product description, disclaimer at the bottom of the page)

 

Table of contents

1. Ivermectin: Discovering the anticancer potential of an antiparasitic drug. 1
2. Introduction. 3
3. Ivermectin – the birth of a powerhouse in medicine. 3
4. Mechanism of action: how does ivermectin work?. 4
5. Mechanisms of antitumour action of ivermectin. 5
6. Induction of apoptosis and cell cycle arrest. 5
7. Inhibition of key cancer signalling pathways.. 6
8. Modulation of the tumour microenvironment. 6
9. Endoplasmic reticulum stress and apoptosis. 7
10. Mitochondrial dysfunction and cancer cell death. 7
11. Modulation of autophagy 7
12. Possible protocols for the treatment of cancer with ivermectin. 8
13. Preclinical and clinical evidence. 8
14. Breast cancer: 8
15. Triple-negative breast cancer (TNBC) 9
16. Regulation of the tumour microenvironment. 10
17. Stomach cancer. 10
18. Tumours of the liver and biliary tract. 11
19. Renal cell carcinoma (RCC) 11
20. Prostate cancer. 12
21. Leukaemia. 13
22. Cervical cancer. 14
23. Ovarian cancer. 14
24. Brain glioma. 15
25. Lung cancer. 16
26. Pancreatic cancer: 17
27. Bladder cancer: 17
28. Head and neck cancer: 17
29. Oesophageal cancer: 18
30. Drug delivery and formulation. 18
31. Nanoparticle-based drug delivery. 18
32. Liposomal Ivermectin. 19
33. Connection to drug carriers.. 19
34. Cancer stem cells and immunity. 19
35. The role of ivermectin against cancer stem cells (CSCs) 19
36. Multidrug resistance (MDR) reversal: 20
37. Ivermectin and the immune system. 20
38. Synergy with immune therapies: 20
39. Effect on tumour-associated macrophages (TAM) 20
40. Comparative analysis. 21
41. Ivermectin versus other reformulated drugs. 21
42. Side effects and toxicity profiles 21
43. Clinical research roadblocks and future research challenges. 22
44. Potential biomarkers of ivermectin sensitivity. 22
45. Preclinical (animal) versus clinical (human) studies 22
46. Combination therapies: Ivermectin with conventional cancer treatments. 23
47. Increasing the effectiveness of chemotherapy: 23
48. Improving the outcome of immunotherapy: 23
49. Overcoming multidrug resistance: 24
50. Reduction in tumour stemness: 24
51. Clinical trials and future prospects. 24
52. Phase II study in glioblastoma multiforme: 25
53. Breast cancer research: 25
54. Colorectal cancer research: 25
55. Other potential studies: 25
56. Conclusions: The way forward for ivermectin in oncology 26
57. References: 26

 

Introduction

Since its discovery and development in the 1970s through the research of two scientists – Japanese microbiologist Satoshi Omura and Irish parasitologist William C. Campbell – ivermectin has evolved wonderfully over time. (1)
This is a „miracle” cure in the true sense of the word, provided it has the potential to combat many diseases, infections, and even fatal conditions such as cancer.
As research continues into the various possible mechanisms of action of Ivermectin, discoveries continue to take place and newer uses of Ivermectin are being introduced into clinical practice. (2)
In summary, since its development as a potent antiparasitic drug for the treatment of parasites, Ivermectin has achieved a transformation of millions through its parasitic disease elimination activities, mainly in developing regions of the world. Contemporary research shows that ivermectin has the potential to act as a drug against several inflammatory diseases and viral infections, prompting scientists to explore its potential for many medical applications. (3)

Ivermectin – the birth of a powerhouse in medicine

The medical industry first recognised ivermectin as an antiparasitic drug thanks to Merck Sharp & Dohme (MSD) in 1981 after the discovery of the substance in the soil bacterium Streptomyces avermitilis. (4)
Following this discovery, scientists and researchers began to carry out tests on humans, observing how well Ivermectin treats parasitic infections in animals, due to its effectiveness in eliminating the infectious process from the infected host. (5)
In the late 1980s, health authorities recommended the use of ivermectin to treat onchocerciasis (river blindness), which affected many people in Africa and South America. (6)
Thus, what started only as an anti-parasitic drug has now become a widely used treatment for several diseases and infections, the most common of which include:

• Strongyloidiasis – intestinal parasitic infection
• Scabies – it is characterised by a mite infestation that spreads rapidly among people.
• Lymphatic filariasis – a parasitic disease transmitted by mosquitoes
• Head lice – as an alternative to conventional treatment methods

Ivermectin has become a global public health tool through mass drug administration programmes that have reduced the impact of parasitic diseases worldwide. This is indeed a very big milestone for this drug. (7)
Since its discovery, Ivermectin has gained widespread public recognition during the COVID-19 pandemic, while maintaining its original role as an important life-saving antiparasitic drug. (8)
The combined research of Dr Satoshi Ōmura and Dr William C. Campbell helped discover ivermectin as a treatment for human and animal parasites, which later led to a Nobel Prize being awarded to them in 2015. (9)

Mechanism of action: How does Ivermectin work?

Ivermectin mainly acts on the nervous system of the parasite that has infested the animal or human host. Once introduced into the body, Ivermectin binds to the parasite's nervous system to eliminate it. (10)
The drug adheres to glutamate-gated chloride channels, triggering the movement of chloride ions, which causes paralysis of the parasite and its eventual death. (11) Lacking the same channels in human cells, Ivermectin is safe for patients when taken as prescribed by a physician. However, long-term exposure to high doses of ivermectin can also adversely affect the receptors of the nervous system in a way that can cause neurotoxic effects in the affected individual. (12)
Similarly, in the world of veterinary medicine, certain dog breeds, such as Australian Shepherds and collie, require special attention when prescribing ivermectin. The reason for this is the lack of protective P-glycoprotein in these particular dog breeds. (13)
A deficiency of this protein makes these dogs susceptible to developing neurotoxicity to Ivermectin, which can lead to harmful consequences such as ataxia, tremors and even coma. (14) Therefore, caution should be exercised before prescribing ivermectin to humans and animals with special conditions or deficiencies, in addition to those mentioned above.
The different biological structures and receptors among organisms mean that Ivermectin affects them in different ways. The drug acts on glutamate-gated chloride channels in worms and lice, as these channels sustain both neural and muscular activity. (13) Chloride permeability increases when the drug binds to glutamate-gated chloride channels and causes paralysis that leads to the death of the parasite.
The absence of these chloride channels in human biology makes the drug safe during permitted use scenarios. Reduced activity of the P-glycoprotein, which regulates the removal of the drug in dogs, leads to their neurological toxicity whenever they encounter Ivermectin. The drug has a different effect on different species because it targets parasites, but causes limited risk to humans and limited effects on some dogs with genetic susceptibility. (14)

Mechanisms of antitumour action of ivermectin

Some of the commonly accepted hypotheses and theories regarding the anticancer effects of ivermectin are discussed below:

Induction of apoptosis and cell cycle arrest

Scientific studies show that ivermectin activates programmed cell death (apoptosis) in various types of cancer cells. (15)
A study by the Anticancer Research Journal found that ivermectin activates apoptosis mechanisms in cancerous colon and breast tissues through the following sequence (16):

• Expression levels of proapoptotic proteins such as Bax become higher with ivermectin treatment.
• Reduction of anti-apoptotic proteins such as Bcl-2
• These enzymes activate caspases, leading to cell destruction.
• Tumour cells stop dividing after ivermectin administration, as the drug stops cell cycle progression in G1 and G2/M phases and blocks tumour growth.

In summary, some medical therapies, together with interventions, have a significant effect on cellular processes that cause cells to change their function. Cell death by apoptosis occurs because Bax expression increases, while Bcl-2 decreases and caspases become active. (16)
Through molecular events, the cell experiences a controlled disassembly process that removes damaged or unwanted cells from the body. The cell cycle can be arrested in the G1 phase or in the G2/M phase due to cell cycle arrest.
Cell cycle progression stops when a cell is arrested in this phase during DNA repair or when proliferation of potentially dangerous cells is halted. Cellular integrity along with avoidance of abnormal cell growth depends on the coordinated actions of apoptosis and cell cycle arrest as critical mechanisms. (15)

Inhibition of key cancer signalling pathways

Many signalling pathways are seen as drivers of cancer development and subsequent progression. (17)
Studies show that ivermectin effectively stops cancer signalling pathways, resulting in reduced tumour growth and expansion and a reduced risk of metastasis. (17)
Signal transduction networks function as essential elements in cancer development, as each network controls essential cellular processes. Tumour growth and invasion take place through the WNT/β-catenin pathway, in which activation of β-catenin leads to the expression of genes that drive tumour cell proliferation and metastasis.
The process of β-catenin activation is inhibited by ivermectin treatment, which limits the growth and proliferation of tumour cells. Survival and resistance to programmed cell death and enhancement of tumour cell growth depend on the PI3K/Akt/mTOR signalling pathway. (17)
The drug Ivermectin interrupts these survival mechanisms of cancer cells and simultaneously induces cell death through apoptosis. The NF-κB signalling pathway regulates inflammation along with metastasis, as these processes are crucial for the spread and progression of cancer. (17)
By reducing inflammation, ivermectin shows the potential to prevent the metastasis of cancer cells, thereby stopping the spread of cancer. Ivermectin shows therapeutic potential in the treatment of cancer by affecting key cell signalling pathways, allowing for more potent cancer cell death.

Modulation of the tumour microenvironment

The tumour microenvironment (TME) plays an important role in cancer resistance to therapies. Studies have shown that ivermectin has the ability to alter the tumour environment, thereby improving their response to cancer treatment. (18)
According to the research, the following findings were noted:

• The immune response becomes more effective against cancer because ivermectin eliminates cells that inhibit immune function. (19)
• An interesting aspect of ivermectin is that it helps to change tumours from a low immune (cold) state to a high immune (hot) state, which energises and enhances the impact of immunotherapeutic processes. (20)

Endoplasmic reticulum stress and apoptosis

Laboratory studies have shown that ivermectin induces endoplasmic reticulum (ER) stress in cancer cells, thereby triggering an unfolded protein response (UPR).
Biological stress imposed on the endoplasmic reticulum both impairs protein handling and activates cell suicide mechanisms that lead to lethal consequences for cancer cells.
Studies show that Ivermectin enhances processes through the ER stress markers CHOP and ATF4 to induce cancer cell death. The ER stress response pathway makes Ivermectin a promising therapeutic approach against cancers that have developed drug resistance.

Mitochondrial dysfunction and cancer cell death

Mitochondria play a key role in the metabolism and survival of cancer cells. Ivermectin disrupts mitochondrial function by inhibiting oxidative phosphorylation and promoting the accumulation of reactive oxygen species (ROS).
This leads to depolarisation of the mitochondrial membrane, release of cytochrome c and activation of caspases, ultimately resulting in apoptosis.
Furthermore, ivermectin has been shown to downregulate mitochondrial fusion proteins, impairing the adaptive responses of cancer cells to metabolic stress. These findings highlight its potential as a metabolic disruptor in oncology.

Modulation of autophagy

Autophagy is a cellular process that cancer cells use to survive under stressful conditions, including chemotherapy and nutrient deprivation. Ivermectin was found to modulate autophagy by inhibiting autophagosome formation and promoting autophagic cell death.
In preclinical studies, ivermectin downregulated autophagy-related proteins such as Beclin-1 and LC3-II, sensitising cancer cells to chemotherapy. This dual action of inhibiting survival autophagy while promoting cytotoxic autophagy makes ivermectin a promising candidate for combination therapies in cancer treatment.
These expanded sections add depth to the existing content, including additional cancer types, drug delivery strategies and mechanistic insights into the anticancer potential of Ivermectin.

Possible protocols for the treatment of cancer with ivermectin

Although ivermectin has no officially recognised cancer treatment protocols, several alternative medicine practitioners have investigated its potential therapeutic value.

• Several doctors, along with research experts, believe that the administration of 12 mg of ivermectin twice a day shows potential benefit in cancer treatment. These anecdotal reports of ivermectin use have no proven benefit in large clinical trials. (21)
• Several doctors in Poland have used Ivermectin together with Fenbendazol and THC (tetrahydrocannabinol) in the combination treatment of certain cancers, according to anecdotal observations. However, more studies are needed to verify both the efficacy and therapeutic properties of Ivermectin. (22) (23)
• Some hypotheses indicate that Ivermectin has the ability to improve the efficacy of traditional chemotherapy or immunotherapy when used as part of their combination treatment. In order to develop official protocols for the use of ivermectin in cancer therapy, further research needs to be conducted along with clinical trials. (16)

 

Preclinical and clinical evidence

Various experiments in laboratory conditions and on animals have shown that Ivermectin exhibits anticancer properties. (16)
As listing all of them may be beyond the scope of this article, it is better to review the anticancer role of ivermectin in some of the world's most common cancers.

Breast cancer:

Breast cancer is one of the most common types of cancer found worldwide. It develops from mutated breast epithelial cells that arise from several carcinogens. (24)
Breast cancer is one of the most common malignancies among women worldwide, and statistics show that a new diagnosis is made every eighteen seconds. (24)
The development of breast cancer depends on genetic susceptibility, hormonal problems, lifestyle habits and exposure to toxins in the environment.
Conventional therapies including surgery in combination with chemotherapy and radiotherapy and targeted therapies are encountering drug resistance and patients are experiencing relapses. (25)
Ivermectin induces specific effects that beneficially control cell growth and proliferation in various cell lines. Laboratory experiments have shown that ivermectin reduces cell proliferation in the human breast cancer cell lines MCF-7, MDA-MB-231 and MCF-10.
By inhibiting the Akt/mTOR pathway, ivermectin blocks an essential cellular mechanism required for cell growth and survival. Through autophagy, ivermectin promotes the breakdown of cellular material and leads to tumour destruction. Through its mechanism of action, ivermectin specifically inhibits the activity of the PAK1 protein, which supports its anti-tumour effect on cell proliferation. (26)
Ivermectin exhibits antiproliferative activity and does not induce apoptotic activation in canine CMT7364 and CIPp cells. Through its ability to block cell cycle progression, it prevents at critical stages and simultaneously blocks the Wnt signalling pathway, which contributes to tumour growth and metastasis.
Through these mechanisms, ivermectin shows its potential as a versatile therapeutic agent in both human and animal models of cancer.

Triple-negative breast cancer (TNBC)

TNBC shows extreme aggressiveness because the disease lacks detectable oestrogen receptors in combination with the absence of progesterone receptors and HER2 protein. (27)
Ivermectin shows promise in the treatment of this type of cancer:

• It mimics SID function by blocking the connection between SID and α-helix 2.
• This mechanism manipulates the EMT E-cadherin gene to reactivate tamoxifen sensitivity in triple-negative breast cancer cases.
• It works by controlling a drug-resistant type of breast cancer stem cell that stimulates tumour growth and disease recurrence. (28)

 

Regulation of the tumour microenvironment

Ivermectin affects the tumour microenvironment in breast cancer patients in the following ways:

• High ATP levels favour greater release of HMGB1 through P2 × 4/P2 × 7/Pannexin-1 channels. (29)
• This substance activates immunogenic death processes mediated by the immune system, along with inflammatory reactions.
• TAMs are modulated by therapy, resulting in a change in their phenotype from M2 to the anti-tumour subtype M1.

Stomach cancer

Gastric cancer is the third most deadly cancer in the world, causing deaths due to its existence and subsequent complications. (30)
Ivermectin exhibits tumour cell inhibitory activity in gastric cells in both laboratory studies and in living organisms of the YAP1 protein, by targeting, thereby enhancing the therapeutic response of MKN1 and SH-10-TC cells expressing YAP1. (31) (32) The drug therefore prevents angiogenesis and blocks the action of important cancer-promoting cytokines.
Studies show that Ivermectin exhibits both inhibition of cell proliferation and increased apoptosis in CC14, CC36, DLD1 and Ls174T cells. The Wnt signalling pathway is blocked by ivermectin, which normally functions to promote tumour growth and survival.
The cycle of tumour cell proliferation is disrupted by Ivermectin treatment, which promotes tumour cell death. (16) The administration of ivermectin in cells leads to increased expression levels of caspase-3, which is involved in apoptotic cell death.
The two mechanisms of Wnt pathway inhibition, together with increased caspase-3 expression, act as a double-edged approach that terminates tumour expansion and activates programmed cell death, thereby positioning Ivermectin as a strong candidate for preventing cancer cell survival. (33)

• Ivermectin targets cancer stem cells (CSCs) to reduce the risk of tumour recurrence and treatment failure.
• The mechanism for preventing metastasis depends on arresting the epithelial-mesenchymal transition (EMT).
• Ivermectin helps to increase the efficacy of 5-FU in combination with oxaliplatin, helping to achieve better results when used as standard therapy. (34)

Tumours of the liver and biliary tract

The biliary tract, together with the liver, is an aggressive malignant tissue that attacks these organs, including the bile ducts and gallbladder. (35) These cancers become difficult to detect in the early stages because they do not produce any detectable signals until they reach the later stages of development.
The most common type of primary liver cancer is hepatocellular carcinoma (HCC), which develops mainly in people with chronic liver disease and hepatitis infections and cirrhosis. (36)
Diagnosis of biliary tract cancer along with gallbladder cancer remains highly lethal as patients develop symptoms too late and treatment options are limited.
Many factors contribute to the development of liver cancer, including obesity, alcohol consumption and hereditary tendencies.
New therapies need attention and early detection screening is becoming essential as improved treatment has not led to improved patient survival outcomes. (37)

• The development of hepatocellular carcinoma in Mob1b-/- mice is arrested as YAP1 activity is blocked by this drug.
• Studies indicate that ivermectin blocks KKU214 cell proliferation and arrests the cell cycle in S phase, while inducing gemcitabine-resistant cell death.
• Reducing tumour progression through fibrosis helps to protect against the negative effects of cirrhosis on tumour formation.

Renal cell carcinoma (RCC)

Renal tubules give rise to renal cell carcinoma, which remains the most common form of kidney cancer. The disease progresses without noticeable symptoms before symptoms such as urine bleeding and pain in the side along with unexpected weight loss. (38)
Risk factors for renal cell carcinoma are smoking and obesity, as well as high blood pressure and family history combined with heredity.
As RCC shows resistance to traditional chemotherapy, surgery is the main treatment option for localised renal cell carcinoma. Targeted therapies along with immunotherapy options become essential when advanced stages of the disease are present. (39)
People who are diagnosed with RCC in a timely manner have better survival outcomes, as late-stage RCC shows worse prognostic factors.
Aggressive renal cell carcinoma remains resistant to standard treatments.
However, even in this case, ivermectin causes specific inhibition of RCC cell lines, allowing normal kidney cells to remain intact:

• Inducing mitochondrial dysfunction.
• Reduction in ATP production.
• Increased expression of HEL (mitochondrial stress marker).
• Combining tyrosine kinase inhibitors with ivermectin treatment improves treatment efficacy.

Prostate cancer

The most common form of cancer in men develops gradually inside the prostate gland, remaining asymptomatic until the later stages of the disease. (40)
Most cases of prostate cancer develop without noticeable symptoms for a long time before late-stage symptoms, such as difficult urination and the presence of blood in the urine and pelvic discomfort, appear. (41)
Older age, hereditary predisposition and inappropriate hormone levels are the main risk factors for this condition.
Prostate cancer occurs on a spectrum of aggressiveness, as many patients reveal such slow-growing tumours that active surveillance proves to be the most appropriate course of action.
The exact treatment depends on the stage of the tumour, although surgical interventions together with hormonal radiotherapy and patients at an advanced stage may require chemotherapy.
Those who undergo PSA testing and digital rectal examination before the onset of symptoms increase their chances of early treatment for prostate cancer.
Expression of the AR-V7 variant responsible for CRPC drug resistance decreases with this treatment. Studies show that Ivermectin exhibits both inhibition of cell proliferation and increased apoptosis in CC14, CC36, DLD1 and Ls174T cells. (42) The Wnt signalling pathway is blocked by ivermectin, which normally acts to promote tumour growth and survival.
The proliferation cycle of tumour cells is disrupted by Ivermectin treatment, which promotes tumour cell death. Ivermectin administration in cells leads to increased expression levels of caspase-3, which is involved in apoptotic cell death.
The two mechanisms of Wnt pathway inhibition, together with increased caspase-3 expression, act as a double-edged approach that terminates tumour expansion and activates programmed cell death, thereby positioning Ivermectin as a strong candidate for preventing cancer cell survival.

Leukaemia

Leukaemia manifests itself as a cancer that attacks both the blood and the bone marrow through the abnormal production of white blood cells.
Leukaemia prevents the body from defending itself against infection while producing blood cells and controlling bleeding. There are several types of leukaemia, with acute and chronic versions of lymphocytic and myeloid leukaemia as distinct subtypes. (43)
Symptoms of leukaemia include fatigue, exhaustion combined with ongoing disease progression and sensitive skin and unexpected weight loss. People contract the disease due to genetic abnormalities combined with exposure to chemicals or radiation, as well as specific viral infections.
Different cancer treatments include chemotherapy along with targeted therapies and bone marrow transplants depending on the stage of leukaemia and the type of leukaemia. Successful treatment outcomes become more feasible when the disease is diagnosed at an early stage.

• Ivermectin shows high specificity against leukaemic cells while maintaining a low level of toxicity to host cells.
• This action increases the amount of chloride ions inside the cells, while making the plasma membrane more negatively charged.
• Ivermectin also triggers ROS production, increasing apoptosis. It also acts synergistically with cytarabine and daunorubicin and helps to enhance their effects. (44)
• The treatment effectively stops tumour expansion in K562 cells that have chronic myeloid leukaemia.
• Treating the tumour microenvironment with a drug improves the recognition capacity of the immune system.

Cervical cancer

Cervical cancer forms inside the cervix, where high-risk strains of human papilloma virus (HPV) remain active as the main cause of the condition. (45)
This cancer develops gradually, starting with precancerous lesions that can be detected by regular PAP smears.
Cervical cancer in its initial stages usually does not produce symptoms, while the advanced form of this disease causes vaginal bleeding and pelvic pain and discomfort during sexual intercourse. (46)
HPV vaccination, combined with regular screening and prompt treatment of precancerous lesions, is effective in reducing the likelihood of developing cervical cancer. Surgery together with radiotherapy and chemotherapy are treatment options for patients depending on the stage of the disease.
Studies indicate that ivermectin shows significant potential in treating cervical cancer cells that use HeLa as their lineage. (47)
This substance blocks cell reproduction while stimulating programmed cell death, which together generate effective tumour cell suppression. The life-cycle blocking mechanism of ivermectin blocks the progression of the G1/S phase, resulting in the activation of the apoptotic pathway.
The treatment process also inhibits the expression of oncogenes E6 and E7, as these genes promote the survival of cervical cancer cells. Studies show that ivermectin has therapeutic value in the treatment of cervical cancer because it acts through these important cellular pathways.

Ovarian cancer

Ovarian cancer is classified as a silent killer because it remains hidden until it spreads to other parts of the body.(48)
Symptoms of bloating, abdominal pain and appetite changes tend to be vague, which can lead people to misdiagnose them as other medical issues.
People with BRCA1 or BRCA2 genetic mutations, together with hereditary cancer risk and hormonal influences, are more susceptible to ovarian cancer. (49)
There is no screening method available for early detection of ovarian cancer, so genetic counselling and prevention strategies become important for those at high risk.
Patients with advanced brain cancer receive combined treatment, which combines surgical removal with chemotherapy, but are increasingly benefiting from targeted medicine. Survival outcomes become much better when cancer patients are detected early at the right stage.

• Inhibits proliferation by inhibiting PAK1 kinase.
• Induces apoptosis through KPNB1-dependent pathways.
• The combined effect of ivermectin with paclitaxel and cisplatin leads to better treatment outcomes.
• Through its mechanism, ivermectin targets cancer stem cells, reducing the risk of disease recurrence

Brain glioma

Gliomas develop within the glial cells of brain tissue, which provide support for nerve cells. The different types of brain tumours vary widely in their development, with slow-growing, low-grade gliomas being the opposite of dangerous gliomas, which are the most deadly subtype. (50)
The symptoms of a brain tumour depend on how far the tumour has spread and where it is located, and can manifest as headaches, as well as seizures and cognitive and neurological disorders such as weakness or loss of vision.
Scientists are still unclear about the causes of brain glioma, but heredity and radiation appear to play a role in its formation.
Gliomas pose a challenge for medical intervention due to their rapid proliferation and resistance to therapeutic approaches, including surgery, radiotherapy and chemotherapy. Researchers continue to conduct studies to develop new therapeutic approaches, such as immunotherapy, to increase patient survival rates. (51)
Research statistics indicate that the survival rate for patients with glioma is between 14 and 17 months to death.
Temozolomide, together with surgery and radiotherapy, is the standard treatment for this type of cancer, although resistance is a major challenge. Ivermectin shows potential by:

• Induction of apoptosis in U87 and T98G cells.
• The Akt/mTOR pathway serves as a treatment target in U251 and C6 glioma cell studies. (52)
• The cellular process of brain microvascular endothelial cells leads to inhibition of tumour angiogenesis by triggering apoptosis.
• The permeability of the blood-brain barrier (BBB) increases under ivermectin treatment, which increases the delivery of the drug across the barrier.

 

RNA helicase inhibition

DDX23 helicase activity appears to be blocked by ivermectin, which inhibits miR-21 function in gliomas, thereby targeting tumour cell growth and proliferation properties. Furthermore, ivermectin also attacks glioma stem cells as they play a role in treatment resistance. (53)

Lung cancer

Studies show that lung cancer consists of two main types, which are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), among the most deadly and aggressive cancers worldwide. (54)
Studies indicate that Ivermectin exhibits anticancer properties in lung cancer cells by activating cell death mechanisms and blocking cell growth, as well as blocking harmful signalling networks. [55]
Ivermectin exhibits anti-NSCLC properties by inhibiting an important Wnt/β-catenin signalling pathway that promotes lung cancer evolution. Studies have shown that ivermectin both disrupts mitochondrial function and provokes reactive oxygen species production, resulting in elevated rates of apoptosis in SCLC models.
Studies have shown that ivermectin acts synergistically with the chemotherapeutic drugs cisplatin and paclitaxel to reduce tumour growth and improve survival statistics.

Pancreatic cancer

Malignant pancreatic cancer is one of the most deadly cancers due to its aggressive behaviour and poor response to standard medical interventions. [56]
Numerous scientific reports show that ivermectin is promising as an additional therapy for pancreatic cancer because it makes cancer cells respond better to chemotherapy. [57]
Preclinical studies on ivermectin show that the drug blocks pancreatic tumour growth by interfering with cellular glucose metabolism and reducing the glycolytic processes that cancer cells need to survive.
Numerous reports indicate that ivermectin is effective against pancreatic cancer stem cells, in addition to its role in improving the efficacy of standard treatment.
Laboratory results indicate that pancreatic cancer patients who receive gemcitabine chemotherapy together with ivermectin experience increased tumour apoptosis along with reduced pathological indices in xenograft models.

Bladder cancer

The anticancer properties of ivermectin are promising for the treatment of urothelial carcinoma, which falls into the category of bladder cancer. (58)
Studies show that Ivermectin blocks survival pathways, including the PI3K/Akt/mTOR signalling cascade, which drives bladder cancer growth. (59)
Studies show that ivermectin has the ability to block the epithelial-mesenchymal transition (EMT), which promotes metastasis of bladder cancer cells and the development of chemo-resistance.
Studies conducted to date suggest that Ivermectin enhances Bacillus Calmette-Guerin (BCG) treatment to kill cancer cells in patients with non-invasive bladder cancer. Additional clinical evaluations and human validation trials need to be conducted to prove the efficacy of this drug in a medical setting.

Head and neck cancer

Malignancies occurring in the tissues of the head and neck, which include squamous cell carcinoma of the oral cavity including the larynx and pharynx, are a challenging group as they show rapid growth and frequent recurrence. (60)
Scientific evidence suggests that ivermectin shows therapeutic potential in head and neck cancers by slowing cell growth and causing tumour death, as well as blocking the growth of blood vessels.
Studies have shown that ivermectin reduces epidermal growth factor receptor (EGFR) activity in head and neck squamous cell carcinoma (HNSCC), as this receptor is usually overexpressed in HNSCC.
Ivermectin makes tumour cells more sensitive to radiotherapy while adjusting their DNA damage response networks. Research is needed to analyse its efficacy as a radiosensitising therapy in patients with squamous cell carcinoma of the head and neck.

Oesophageal cancer

Survival rates for patients with oesophageal cancer remain drastically unfavourable, along with poor diagnosis at detectable stages.
Laboratory studies have shown the usefulness of ivermectin in the treatment of oesophageal cancer, as it prevents cell expansion while increasing programmed tumour cell death.
Cancer cell death increases when Ivermectin activates a dual mechanism that affects oxidative stress and mitochondrial dysfunction in cells. Recent studies indicate that Ivermectin causes oesophageal tumours to reduce markers of cancer stem cells, thereby minimising tumour recurrence. (61)
Clinical trials are currently being conducted to combine ivermectin with fluoropyrimidines and platinum-based compounds as standard cancer treatments.

Drug delivery and formulation

Nanoparticle-based drug delivery

The availability of ivermectin for cancer treatment is improving as researchers develop advanced drug delivery platforms using liposomal and nanoparticle formulations.
Ivermectin achieves enhanced delivery to tumour sites, as well as prolonged circulation time and improved solubility due to nanoparticle health systems.
Current research shows that nanotechnology-based ivermectin formulations enable better uptake of the drug by cancer cells and minimise unintended consequences.
The administration of ivermectin via these precise methods works to increase both the effectiveness of the treatment and minimise unwanted side effects throughout the body.

Liposomal Ivermectin

Researchers have developed liposomal versions of ivermectin to achieve both pharmacological potentiation and stronger anti-cancer effects. (62)
Protection of the drug by liposomal encapsulation results in both a longer half-life and increased accumulation of the drug in tumour tissue.
Current laboratory studies show that liposomal Ivermectin protects normal tissues from harmful effects by inducing apoptosis of cancer cells.

Connection to drug carriers

The use of polymer micelles and dendrimers serve as carriers for ivermectin to ensure controlled delivery of the drug and improved therapeutic outcomes for cancer patients.
Drug delivery systems improve ivermectin's ability to treat cancer by eliminating obstacles related to drug solubility and increasing therapeutic efficacy.

Cancer stem cells and immunity

The role of ivermectin against cancer stem cells (CSCs)

The anticancer properties of ivermectin transform it into an effective therapy against cancer stem cells (CSCs).
Cancer recovery occurs through specialised cells known as cancer stem cells (CSCs), which are responsible for creating new tumours along with their ability to spread and survive various treatments.
Cancer stem cells represent a major hurdle for oncology because they have unlimited reproductive potential and are resistant to traditional cancer treatments. (63)
Ivermectin destroys cancer stem cells through its ability to block Wnt/β-catenin and Hedgehog signalling mechanisms that sustain the presence and proliferation of CSCs.
Treatment efficacy is enhanced and prevention of tumour recurrence occurs because Ivermectin intervenes in those signalling pathways that maintain stem cell characteristics in cancer cells. Ivermectin shows potential use as a complementary drug to combat drug resistance, as it inhibits ABC transporter function in CSCs.

Multidrug resistance reversal (MDR)

Cancer cells develop multidrug resistance through active transport using efflux transporters, allowing them to effectively pump out drugs, becoming a key barrier to chemotherapy treatment. (64)
Ivermectin effectively halts the function of P-glycoprotein (P-gp), as well as other ATP-binding transporters (ABCs) that lead to MDR in various tumour types.
Combining Ivermectin treatment with chemotherapeutic drugs leads to better outcomes, as the drug blocks the ejection pumps that normally pump out these drugs. The additive effects of Ivermectin with conventional cancer chemotherapy drugs confirm its potential to become an effective treatment strategy for penetrating MDR.

Ivermectin and the immune system

Synergy with immune therapies

Recent studies show that ivermectin acts as an immune regulator, making it suitable for supporting immunotherapy.
Studies show that ivermectin enhances the action of immune checkpoint inhibitor drugs, such as anti-PD-1 and anti-CTLA-4, by restoring immunosuppression of the tumour environment.
Activation of cytotoxic T cells increases, while dendritic cells increase antigen presentation, as Ivermectin simultaneously reduces the number of regulatory T cells that suppress immune responses.
Ivermectin modifies immune pathways, through which it can turn immunologically „cold” tumours into „hot” ones, which increases their response to immunotherapy.

Effect on tumour-associated macrophages (TAM)

Immune cells known as tumour-associated macrophages (TAMs) have two different functions in cancer cells, as they can either support tumours through the M2 phenotype or help fight tumours through the M1 phenotype.
Ivermectin shows the ability to convert TAMs with pro-tumour M2 functions into anti-tumour M1 cells, resulting in stronger immune monitoring and tumour destruction.
The macrophage polarisation effect generated by ivermectin treatment creates an immunostimulatory context that improves the efficacy of existing immunotherapeutic approaches.

Comparative analysis

Ivermectin versus other reformulated drugs

A number of drugs from a variety of sources, such as metformin, hydroxychloroquine and fenbendazol, have been evaluated as potential anticancer drugs n.

• Patients with diabetes use metformin as their primary drug, but studies show its anti-diabetic properties by inhibiting mTOR signalling while reducing insulin-like growth factor (IGF) activity.
• Metformin acts on the metabolic cascade, but Ivermectin acts through two different mechanisms involving apoptosis induction and immune modulation.
• Hydroxychloroquine has an antimalarial capacity that shows the potential to stop autophagy in cancer cells to improve the efficacy of chemotherapy.
• The antitumour properties of hydroxychloroquine differ from ivermectin, as it does not show a significant effect on CSCs or reverse MDR.
• Fenbendazol has shown anti-tumour properties due to its dual action of microtubule disruption combined with inhibition of glucose uptake when developed as an anti-parasitic drug.
• The main target of treatment with fenbendazolem is metabolic processes and its therapeutic scope appears to be more limited than with ivermectin.

Side effects and toxicity profiles

It is well known that ivermectin has a safe profile, but administrators must still consider its potential unknown effects when used in high doses.
Potential toxic effects include:

• Excessive intake of ivermectin may modify GABA-gated chloride channel function, resulting in dizziness along with ataxia and mental confusion.
• Medical evidence suggests that taking ivermectin for a prolonged period of time may cause a mild increase in liver enzymes.
• The drug Ivermectin has the potential to modify drug metabolism through interaction with cytochrome P450 substrate drugs.
• Clinical trials on appropriate doses of ivermectin for cancer treatment should continue, as the drug shows a higher level of safety compared to typical chemotherapy drugs.

Clinical research roadblocks and future research challenges

In conducting clinical trials, Ivermectin has encountered major hurdles when moving from preclinical data to clinical practice. The lack of large-scale randomised controlled trials (RCTs) prevents regulatory authorities from approving the use of this drug.
The generic nature of Ivermectin prevents pharmaceutical companies from finding sufficient financial reasons to initiate clinical trials. There has been resistance from the oncology community to accept Ivermectin as an anti-cancer therapy due to ongoing debates about its uses in COVID-19 treatment.

Potential biomarkers of ivermectin sensitivity

Identification of biomarkers capable of predicting response to ivermectin will lead to better patient selection in future studies.

Potential biomarkers include:

• Wnt/β-catenin mutations in ivermectin-sensitive tumours. Measurement of P-glycoprotein expression levels demonstrates the ability to reverse MDR. Study of immune patterns to predict compliance with checkpoint blockers.
• Researchers should now direct research to develop specific strategies that integrate these biomarkers with specific ivermectin-based models of care to ensure optimal outcomes for patients using this therapy.

Preclinical (animal) versus clinical (human) studies

The potential of ivermectin as an anticancer drug needs to be assessed based on a clear distinction between laboratory animal studies and human clinical trials. The table below identifies the key differences between the two studies.

Combination therapies: Ivermectin with conventional cancer treatments

The use of ivermectin shows the most promising potential as a device that enhances conventional anticancer therapies in combination. Ivermectin targets multiple pathways of cancer progression, thus demonstrating the ability to enhance current anticancer therapies while preventing therapeutic resistance.
Some of the different mechanisms of action of ivermectin in combination with standard cancer treatments are listed below:

Increasing the effectiveness of chemotherapy

Research shows that ivermectin treatment increases the sensitivity of cancer cells to standard chemotherapeutic drugs – doxorubicin and paclitaxel along with cisplatin.
Preventing cancer cell survival becomes possible because Ivermectin blocks important pathways such as PI3K/Akt/mTOR signalling, while causing oxidative damage to cancer cells.
Chemotherapy treatment in cancer patients leads to increased cell apoptosis, allowing for lower drug doses and reduced toxicity to healthy tissues.

Improving the outcome of immunotherapy

The immune system benefits from the administration of ivermectin because it modifies immune responses, which enhances the efficacy of the immune checkpoint inhibitors PD-1 and CTLA-4.
The combination of enhancing T-lymphocyte activation and decreasing immunosuppression of the tumour microenvironment through ivermectin administration enables better defence of cancer cells in the human body. Studies show that ivermectin helps mature dendritic cells while improving antigen presentation, thereby enhancing anti-tumour defence.

Overcoming multidrug resistance

A major obstacle during anti-cancer therapy is the development of cancer cell resistance to various drugs.
Ivermectin has been shown to be effective in slowing down the efflux pump activity of drugs, including P-glycoprotein together with ABC transporters, which remove chemotherapeutic substances from tumour cells.
The efficacy of chemotherapeutic drugs against resistant tumours improves with treatment with ivermectin, as the drug prevents the elimination of chemotherapeutic agents by tumour cells.

Reduction in tumour stemness

A small subset of cancer stem cells called CSCs enable tumour stemness to persist, contributing to drug resistance, spread and relapse.
Recent findings show that Ivermectin acts as a specific inhibitor of CSC-like properties due to its ability to suppress Wnt/β-catenin and Hedgehog signalling and matrix-associated markers. Destruction of CSCs by Ivermectin treatment would enhance conventional therapies, reducing both relapse rates and improving patient survival statistics.
When used in combination, these different treatments offer new opportunities to develop therapies that can improve health outcomes for patients in many types of cancer.
Additional research is needed to confirm these findings along with the development of optimal drug protocols using Ivermectin in medicine.

Clinical trials and future prospects

Following promising preliminary laboratory results on the anticancer properties of ivermectin, targeted human clinical trials should be conducted to test its safety limits, as well as the most effective doses and treatment potential in humans.
Researchers are conducting a number of clinical trials and are preparing additional research projects to evaluate ivermectin treatment for different types of cancer.

Phase II study in glioblastoma multiforme

Researchers are conducting a phase II clinical trial of ivermectin for the treatment of patients with glioma, evaluating treatment outcomes, including tumour size reduction along with medical survival time. (65)
Studies investigating ivermectin as a potential therapy for glioblastoma multiforme must be carried out immediately, as the disease is aggressive and standard drugs do not provide adequate control.

Breast cancer research

Medical researchers are conducting studies combining ivermectin with conventional breast cancer chemotherapy protocols.
The study aims to see how Ivermectin affects tumour growth, as well as chemotherapy response rates and patient survival time. Ivermectin is showing evidence of overcoming some of the resistance factors that some studies claim reduce the effectiveness of current treatment options.

 Research into colorectal cancer

Researchers conducted a colorectal cancer study using ivermectin, combining the drug with EGFR and VEGF inhibitors.
Research experts are testing Ivermectin to increase the potency of primary drugs, while assessing its ability to minimise the spread of cancer cells and increase treatment efficacy. Such successful results would establish Ivermectin as an important therapeutic agent for the treatment of colorectal cancer. (66)

Other potential studies

Additional studies are using ivermectin to determine its effect on pancreatic cancer, lung cancer and various forms of leukaemia and lymphoma in early clinical trials. The drug shows unique potential in oncology as it affects several different cancer-causing pathways.
The results of the clinical trials will serve as the primary criteria for determining whether Ivermectin can achieve widespread clinical use in oncology treatment. Before ivermectin can become a common option for cancer treatment, regulatory approval must be granted by medical authorities through safety testing and extensive clinical trials.

Conclusions: The way forward for ivermectin in oncology

Initially recognised as an anti-parasitic drug, ivermectin has recently gained interest as a potential therapeutic agent for the treatment of cancer. Scientific evidence shows that ivermectin induces cell death while maintaining the cell cycle and influencing immune responses, which accounts for its potential value in cancer treatment.
Clinical interest in ivermectin as an anti-cancer therapy has grown because it counteracts tumour growth and enhances standard treatment effects, while attacking the underlying cancer immunity and immune evasion mechanisms.
Current laboratory studies show that ivermectin is effective against several types of cancer, including lung cancer, breast cancer, gliomas and leukaemias. The medical use of ivermectin in the treatment of cancer requires extensive clinical trial results to establish safe dosing recommendations along with standard anticancer drug evaluations.
Despite its potential, challenges remain. Finances have not been sufficient motivation for pharmaceutical companies to conduct clinical trials, as Ivermectin falls into the generic category. An in-depth evaluation of the drug's response and side effects, as well as individual patient responses to treatment, is needed.
Detailed safety assessments and pharmacokinetic testing by pharmaceutical companies will determine the most favourable route for incorporating ivermectin into cancer treatment. Researchers are actively pursuing ongoing studies that explore the tumour suppressive potential of Ivermectin and its effects on immune responses, as well as mechanisms for reversing drug resistance.
The therapeutic potency and bioavailability of ivermectin could be improved by developing sophisticated nanoparticle-based dosing regimens together with liposomal formulations. Selecting appropriate biomarkers for therapy would increase efficacy rates while reducing treatment risks.
Exploring the applications of Ivermectin in cancer treatment is an active area of promising future research. Comprehensive scientific testing would allow Ivermectin to become an important anti-cancer drug that could provide new perspectives for patients struggling with resistant forms of cancer.

Disclaimer

This article has been written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest using chemical reagents on humans - this is prohibited by law. For a product to be used for treatment, it must be registered as a medicine. The information contained in the text is based on available scientific research and is not intended as medical advice or to promote self-medication. The reader should consult a qualified health professional for all health and treatment decisions.

References:

 

1. O’Malley PA. Ivermectin. Clin Nurse Spec CNS. 2022;36(1):16-9.
2. CRUMP A, ŌMURA S. Ivermectin, „wonder drug” from Japan: the human use perspective. Proc Jpn Acad Ser B Phys Biol Sci. 2011 Feb 10;87(2):13-28.
3. Kaur B, Blavo C, Parmar MS. Ivermectin: A multifaceted drug with potential beyond antiparasitic therapy. Cureus. 16(3):e56025.
4. Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN, Pena L. Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. J Controlled Release. 2021 Jan 10;329:758-61.
5. Laing R, Gillan V, Devaney E. Ivermectin - old drug, new tricks? Trends Parasitol. 2017 Jun;33(6):463-72.
6. González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ. The Pharmacokinetics and Interactions of Ivermectin in Humans-A Mini-review. AAPS J. 2008 Jan 25;10(1):42-6.
7. Park J, Chae JB, Kim S, Yu DH, Kim HC, Park BK, et al. Evaluation of the efficacy of ivermectin against Theileria orientalis infection in grazing cattle. BMC Vet Res. 2019 Aug 17; 15 (1): 297.
8. Song Z, Shi S, Zhang Y. Ivermectin in the treatment of COVID-19: A systematic review and meta-analysis. Heliyon. 2024 Mar 11;10(6):e27647.
9. Buonfrate D, Chesini F, Martini D, Roncaglioni MC, Ojeda Fernandez ML, Alvisi MF, et al. High-dose ivermectin for early treatment of COVID-19 (COVER study): A randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Int J Antimicrob Agents. 2022 Feb;59(2):106516.
10. Bryant A, Lawrie TA, Dowswell T, Fordham EJ, Mitchell S, Hill SR, et al. Ivermectin in the prevention and treatment of COVID-19 infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines. Am J Ther. 2021 Jun 21;28(4):e434-60.
11. Zaidi AK, Dehgani-Mobaraki P. Mechanisms of action of ivermectin against SARS-CoV-2 – a comprehensive review. J Antibiot (Tokyo). 2022;75(2):60-71.
12. Johnson-Arbor K. Ivermectin: a mini review. Clin Toxicol Phila Pa. 2022 May;60(5):571-5.
13. Nagao I, Nakazawa M, Tachibana Y, Kawasaki M, M Ambrosini Y. Assessment of P-glycoprotein function using epithelial interfaces derived from canine intestinal organoids. Xenobiotica Fate Foreign Compd Biol Syst. 2024 Jun;54(6):342-9.
14. Mealey KL, Owens JG, Freeman E. P-glycoprotein deficiency in dogs and cats: What we know and where we need to go. J Vet Pharmacol Ther. 2023 Jan;46(1):1-16.
15. Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multi-target drug ivermectin: from antiparasitic agent to repositioned anticancer drug. Am J Cancer Res. 2018 Feb 1;8(2):317-31.
16. Tang M, Hu X, Wang Y, Yao X, Zhang W, Yu C, et al. Ivermectin, a potential anticancer drug derived from an antiparasitic drug. Pharmacol Res. 2021 Jan; 163: 105207.
17. Dou Q, Chen HN, Wang K, Yuan K, Lei Y, Li K, et al. Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. Cancer Res. 2016 Aug 1; 76 (15): 4457-69.
18. Lotfalizadeh N, Gharib A, Hajjafari A, Borji H, Bayat Z. The Anticancer Potential of Ivermectin: Mechanisms of action and therapeutic implications. J Lab Anim Res. 2022 Dec 25; 1 (1): 52-9.
19. Huang H, He Q, Guo B, Xu X, Wu Y, Li X. Advances in diversion of antiparasitic drugs for cancer treatment. Drug Des Devel Ther. 2021;15:2747-67.
20. Li YQ, Zheng Z, Liu QX, Lu X, Zhou D, Zhang J, et al. Repositioning antiparasitic drugs in cancer treatment. Front Oncol. 2021 Apr 29;11:670804.
21. Jiménez-Gaona, Y., Vivanco-Galván, O., Morales-Larreategui, G., Cabrera-Bejarano, A., & Lakshminarayanan, V. (2023). Results of ivermectin in cancer treatment: An Experience in Loja-Ecuador. Nursing reports (Pavia, Italy), 13(1), 315-326. https://doi.org/10.3390/nursrep13010030
22. Baghli, I. (2024). Targeting the mitochondrial-cell junction in cancer treatment: A hybrid orthomolecular protocol. J Orthomol Med, 39
23. Zhou, S., Wu, H., Ning, W., Wu, X., Xu, X., Ma, Y., … & Wang, J. (2021). Ivermectin has a new application in inhibiting colorectal cancer cell growth. Frontiers in Pharmacology, 12, 717529.
24. Menon G, Alkabban FM, Ferguson T. Breast Cancer. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Feb . Available from: http://www.ncbi.nlm.nih.gov/books/NBK482286/
25. Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast Cancer-Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. Cancers. 2021 Aug 25;13(17):4287.
26. Mayrovitz HN, editor. Breast Cancer [Internet]. Brisbane (AU): Exon Publications; 2022 [cited 2025 Feb . Available from: http://www.ncbi.nlm.nih.gov/books/NBK583818/
27. Liu, J., Liang, H., Chen, C., Wang, X., Qu, F., Wang, H., Yang, K., Wang, Q., Zhao, N., Meng, J., & Gao, A. (2019). Ivermectin induces autophagy-mediated cell death via AKT/mTOR signalling pathway in glioma cells. Bioscience Reports, 39(12), BSR20192489. https://doi.org/10.1042/BSR20192489
28. Aysola, K., Desai, A., Welch, C., Xu, J., Qin, Y., Reddy, V., Matthews, R., Owens, C., Okoli, J., Beech, D. J., Piyathilake, C. J., Reddy, S. P., & Rao, V. N. (2013). Triple Negative Breast Cancer – An Overview. Hereditary genetics: current research, 2013(Suppl 2), 001. https://doi.org/10.4172/2161-1041.S2-001
29. Bansal, N., Bosch, A., Leibovitch, B., Pereira, L., Cubedo, E., Yu, J., Pierzchalski, K., Jones, J. W., Fishel, M., Kane, M., Zelent, A., Waxman, S., & Farias, E. (2016). Blocking the PAH2 domain of Sin3A inhibits tumourigenesis and confers retinoid sensitivity in triple-negative breast cancer. Oncotarget, 7(28), 43689-43702. https://doi.org/10.18632/oncotarget.9905
30. Hashimoto, H., Messerli, S. M., Sudo, T., & Maruta, H. (2009). Ivermectin inactivates the kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumour cell lines. Drug discoveries & therapeutics, 3(6), 243-246.
31. Sitarz, R., Skierucha, M., Mielko, J., Offerhaus, G. J. A., Maciejewski, R., & Polkowski, W. P. (2018). Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer management and research, 10, 239-248. https://doi.org/10.2147/CMAR.S149619
32. Nambara, S., Masuda, T., Nishio, M., Kuramitsu, S., Tobo, T., Ogawa, Y., Hu, Q., Iguchi, T., Kuroda, Y., Ito, S., Eguchi, H., Sugimachi, K., Saeki, H., Oki, E., Maehara, Y., Suzuki, A., & Mimori, K. (2017). Antitumor effect of the antiparasitic agent ivermectin via inhibition of Yes-related protein 1 expression in gastric cancer. Oncotarget, 8(64), 107666-107677. https://doi.org/10.18632/oncotarget.22587.
33. Nambara, S., Masuda, T., Nishio, M., Kuramitsu, S., Tobo, T., Ogawa, Y., … & Mimori, K. (2017). Anti-tumour effect of the antiparasitic agent ivermectin through the inhibition of Yes-associated protein 1 expression in gastric cancer. Oncotarget, 8(64), 107666.
34. Wu, X., Deng, G., Hao, X., Li, Y., Zeng, J., Ma, C., He, Y., Liu, X., & Wang, Y. (2014). A caspase-dependent pathway is involved in Wnt/β-catenin signalling promoting apoptosis in Bacillus Calmette-Guerin-infected RAW264.7 macrophages. International Journal of Molecular Sciences, 15(3), 5045-5062. https://doi.org/10.3390/ijms15035045
35. Jonker, D., Rumble, R. B., Maroun, J., & Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care (2006). The role of oxaliplatin in combination with 5-fluorouracil and folinic acid in the first- and second-line treatment of advanced colorectal cancer. Current oncology (Toronto, Ont.), 13(5), 173-184. https://doi.org/10.3747/co.v13i5.99.
36. Oneda, E., Abu Hilal, M., & Zaniboni, A. (2020). Biliary tract cancer: Current medical treatment strategies. Cancers, 12(5), 1237. https://doi.org/10.3390/cancers12051237
37. Asafo-Agyei KO, Samant H. Hepatocellular carcinoma. [Updated 2023 June 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
38. Ruff, S. M., Cloyd, J. M., & Pawlik, T. M. (2023). Annals of Surgical Oncology Practice Guidelines Series: management of primary liver and biliary tract tumours. Annals of surgical oncology, 30(13), 7935-7949. https://doi.org/10.1245/s10434-023-14255-z.
39. Pandey J, Syed W. Renal cell carcinoma. [Updated 2024 October 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK558975/
40. Cardenas, L. M., Sigurdson, S., Wallis, C. J. D., Lalani, A. K., & Swaminath, A. (2024). Advances in the treatment of renal cell carcinoma. CMAJ: Canadian Medical Association Journal = Journal de l’Association médicale canadienne, 196(7), E235-E240. https://doi.org/10.1503/cmaj.230356
41. Leslie SW, Soon-Sutton TL, Skelton WP. Prostate cancer. [Updated 2024 October 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
42. Rosario E, Rosario DJ. Localized prostate cancer. [Updated 2022 September 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK563248/
43. Melotti, A., Mas, C., Kuciak, M., Lorente-Trigos, A., Borges, I., & Ruiz and Altaba, A. (2014). The river blindness drug Ivermectin and related macrocyclic lactones inhibit the WNT-TCF pathway response in human cancer. EMBO molecular medicine, 6(10), 1263-1278. https://doi.org/10.15252/emmm.201404084
44. Chennamadhavuni A, Lyengar V, Mukkamalla SKR, et al. Leukaemia. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
45. Zhang, Y., Sun, T., Li, M., Lin, Y., Liu, Y., Tang, S., & Dai, C. (2022). Ivermectin-Induced Apoptotic Cell Death in Human SH-SY5Y Cells Involves the Activation of Oxidative Stress and Mitochondrial Pathway and Akt/mTOR-Pathway-Mediated Autophagy. Antioxidants (Basel, Switzerland), 11(5), 908. https://doi.org/10.3390/antiox11050908.
46. Fowler JR, Maani EV, Dunton CJ, et al. Cervical cancer. [Updated 2023 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
47. Zhang, S., Xu, H., Zhang, L., & Qiao, Y. (2020). Cervical cancer: Epidemiology, risk factors and screening. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 32(6), 720-728. .
48. Li, N., & Zhan, X. (2020). The antiparasitic drug ivermectin can inhibit ovarian cancer by regulating the lncRNA-EIF4A3-mRNA axis. EPMA journal, 11(2), 289-309. https://doi.
49. Matulonis, U. A., Sood, A. K., Fallowfield, L., Howitt, B. E., Sehouli, J., & Karlan, B. Y. (2016). Ovarian cancer. Nature reviews. Disease primers, 2, 16061. https://doi.
50. Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2023 Sep 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. available at: https:
51. Mesfin FB, Karsonovich T, Al-Dhahir MA. Gliomas. [Updated 2024 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
52. Davis M. E. (2016). Glioblastoma: An overview of the disease and treatment. Clinical journal of oncology nursing, 20(5 Suppl), S2-S8. .
53. Bahmad, H. F., Mouhieddine, T. H., Chalhoub, R. M., Assi, S., Araji, T., Chamaa, F., Itani, M. M., Nokkari, A., Kobeissy, F., Daoud, G., & Abou-Kheir, W. (2018). The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioma and immature neuroblastoma. Oncotarget, 9(71), 33549-33561. https://doi.
54. Aljardali, M. W., Kremer, K. M., Parker, J. E., Fleming, E., Chen, H., Lea, J. S., Kraus, W. L., & Camacho, C. V. (2024). Nucleolar localization of the RNA helicase DDX21 predicts survival outcomes in gynecologic cancers. Cancer research communications, 4(6), 1495-1504. https://doi.
55. Siddiqui F, Vaqar S, Siddiqui AH. Lung cancer. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
56. Li, M. Y., Zhang, J., Lu, X., Zhou, D., Deng, X. F., Liu, Q. X., Dai, J. G., & Zheng, H. (2024). Ivermectin induces nonprotective autophagy via downregulation of PAK1 and apoptosis in lung adenocarcinoma cells. Cancer chemotherapy and pharmacology, 93(1), 41-54. https://doi.org/10.1007/s00280-023-04589-6
57. Puckett Y, Garfield K. Pancreatic cancer. [Updated 2024 September 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
58. Lee, D. E., Kang, H. W., Kim, S. Y., Kim, M. J., Jeong, J. W., Hong, W. C., Fang, S., Kim, H. S., Lee, Y. S., Kim, H. J., & Park, J. S. (2022). Combination treatment with ivermectin and gemcitabine induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction. Frontiers in pharmacology, 13, 934746. https://doi.
59. Leslie SW, Soon-Sutton TL, Aeddula NR. Bladder cancer. [Updated 2024 Aug 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available at: https:
60. Sathe, A., & Nawroth, R. (2018). Targeting the PI3K/AKT/mTOR pathway in bladder cancer. Methods in molecular biology (Clifton, N.J.)., 1655, 335-350. .
61. Johnson, D. E., Burtness, B., Leemans, C. R., Lui, V. W. Y., Bauman, J. E., & Grandis, J. R. (2020). Squamous cell carcinoma of the head and neck. Nature reviews. Disease primers, 6(1), 92. https://doi.org/10.1038/s41572-020-00224-3
62. Xu, N., Lu, M., Wang, J., Li, Y., Yang, X., Wei, X., Si, J., Han, J., Yao, X., Zhang, J., Liu, J., Li, Y., Yang, H., & Bao, D. (2021). Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway. BMC cancer, 21(1), 1307. https://doi.
63. Kar, B., Mahanti, B., Kar, A. K., Mazumder, R., Roy, A., & Majumdar, S. (2024). Nanoliposome gel-based ivermectin topical delivery system: Fabrication, characterization, in vivo and in vitro studies. Intelligent Pharmacy.63 Bisht, S., Nigam, M., Kunjwal, S. S., Sergey, P., Mishra, A. P., & Sharifi-Rad, J. (2022). Cancer stem cells: From insights into the fundamentals to recent advances and therapeutic targets. Stem cells international, 2022, 9653244. https://doi.
64. Xue, X., & Liang, X. J. (2012). Overcoming drug efflux-based multidrug resistance in cancer with nanotechnology. Chinese journal of cancer, 31(2), 100-109. .
65. Bagley S. J. (2023). Phase II trials in the era of immunotherapy for glioblastoma multiforme: Novel mechanisms of action, known challenges in study design and assessment of tumour response. Neuro-oncology, 25(6), 1098-1099. https://doi.
66. Zhou, S., Wu, H., Ning, W., Wu, X., Xu, X., Ma, Y., Li, X., Hu, J., Wang, C., & Wang, J. (2021). Ivermectin has a novel application in inhibiting colorectal cancer cell growth. Frontiers in pharmacology, 12, 717529. https://doi.