Repurposing anti-fungal Itraconazole as an anti-cancer agent

Itraconazole is a broad spectrum antifungal drug shown in various research studies to increase cancer-free progression, increase cancer survival and reduce chemo-resistance; it has effects against mTor and the AMPK pathway in many cancers such as NHL, NSCLC, pancreatic cancer, prostate cancer, endometrial cancer and breast cancer including TNBC.

Itraconazole (ITZ) is a common antifungal drug developed in the 1980s and known to be safe in humans. There is a review of its overall benefits here (1). It is also seen as a drug of great anti-cancer potential by researchers in the ReDo project.

ITZ has recent phase II clinical trials on its ability to limit cancer progression and increase overall survival in non-small cell lung cancer, NSCLC (2),

There is also research against B-Cell Non-Hodgkin’s Lymphoma (3) showing that it also reduces 'chemo-resistance'. Several studies have shown the ability to block mTOR , prevent chemo-resistance and increase survival times (e.g. in Mantle Cell Lymphoma, often confused with NHL). In 2011 Benjamin Nacev showed that it inhibited VEGF and VEGFR (4).

There was a 2013 Clinical Trial with prostate cancer that had spread. Progression-free survival increased and the results seemed dose dependent (600 mg per day producing 48% PFS; 200mg producing 11.8% at 24 weeks). A summary of the drug’s abilities to extend survival in prostate cancer in Phase II clinical trials is here:(5)

Several studies have also shown that this anti-fungal drug can inhibit the Hedgehog signalling pathway. What’s that? It’s the pathway (actually an array of signalling proteins) that turn (differentiate) embryonic cells into lung cells, kidney cells, liver cells etc. When the pathways goes wrong it can lead to chronic illness including cancer (6).

And there's research showing it can limit Cervical cancer spread (7).

There is research showing that ITZ can inhibit proliferation, AMPK and mTOR in endometrial cancer cells(8); and with breast cancer and TNBC (9).

Finally there are several studies with Pancreatic cancer. First there is a 'Case Report' of a patient who could not have surgery and with failing chemotherapy, taking Itraconozole for 9 months and improving the chemo so much that surgery became possible(10). There is 2018 research that shows ITZ can cause apoptosis (cancer cell death) through activation of the Bak-1 pathway (11).  What is interesting is that ITZ is an anti-fungal drug, and carcinogenesis in pancreatic cancer has been shown to be linked to a fungus -

Go to: Fungi promote Pancreatic cancer development 

Researchers in the ReDo project (12) felt the drug may clash with monoclonal antibodies. However their view on the whole was extremely positive for Itraconozole as an anticancer drug.

Go to: 'Safe' Dipyridamole stops platelets helping cancer grow and spread

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References

1. Review - https://www.spandidos-publications.com/ol/14/2/1240
2. NSCLC - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206167/
3. NHL - http://www.bloodjournal.org/content/128/22/5138
4. mTOR and AMPK - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703001/
5. Prostate cancer - http://theoncologist.alphamedpress.org/content/18/2/163
6. Review - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406527/
7. Cervical Cancer - https://www.ncbi.nlm.nih.gov/pubmed/28668841
8. Endometrial cancer - https://www.ncbi.nlm.nih.gov/pubmed/28179296
9. Breast cancer - https://www.sciencedirect.com/science/article/abs/pii/S0304383516306656
10. Pancreatic cancer - https://journals.sagepub.com/doi/abs/10.1177/1078155215572931?journalCode=oppa
11. Pancreatic cancer - https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.27719
12. ReDo project - https://ecancer.org/en/journal/article/521-repurposing-drugs-in-oncology-redo-itraconazole-as-an-anti-cancer-agent