The Potential of Itraconazole: A Cancer-fighting Powerhouse
Since its inception in the 1980s, Itraconazole (ITZ) has carved its niche as an efficacious antifungal medication. But in recent years, an intriguing role for this seasoned drug has begun to take shape. A groundswell of research is championing Itraconazole's potential as an impactful anti-cancer agent, thanks to its multi-faceted attack on diverse pathways involved in cancer pathogenesis.
Undoubtedly, the safety profile of ITZ, established through decades of clinical use, paves the way for its repurposing in the cancer arena. The ReDo project, a leading force in drug repurposing, sees ITZ as an up-and-coming heavyweight in the fight against cancer, citing a flurry of promising research (12).
Non-small cell lung cancer (NSCLC), one of the most prevalent and deadly cancers, has shown a particularly encouraging response to ITZ therapy. Phase II clinical trials have exhibited the drug's ability to stifle cancer progression and bolster overall survival rates in NSCLC patients (2).
An equally promising role has been illuminated for ITZ in combating B-Cell Non-Hodgkin’s Lymphoma. Notably, the drug has shown the capacity to counteract chemo-resistance, a significant hurdle in successful cancer treatment. This unprecedented ability could be attributed to ITZ's knack for blocking mTOR and inhibiting VEGF and VEGFR, ultimately extending survival times (3,4).
In advanced prostate cancer, the application of ITZ seems to take on a dose-dependent effectiveness. High-dose treatment has seen significant improvements in progression-free survival, highlighting the drug's potential in combating this challenging malignancy (5).
ITZ has also demonstrated a unique ability to impede the Hedgehog signaling pathway, a crucial developmental pathway that, when dysregulated, can propel chronic illnesses, including cancer. The blockade of this pathway by ITZ unveils yet another anti-cancer facet of this versatile drug (6).
Furthermore, recent findings suggest ITZ can limit cervical cancer spread (7) and curtail endometrial cancer cell proliferation by disrupting AMPK and mTOR pathways (8). The drug also holds promise in the fight against breast cancer, including the notoriously aggressive triple-negative breast cancer (TNBC) (9).
Lastly, in the case of pancreatic cancer, ITZ has shown intriguing potential. Anecdotal reports and research reveal that the drug can, not only improve the effectiveness of chemotherapy, but also induce cancer cell death through the activation of the Bak-1 pathway (10,11). Notably, pancreatic carcinogenesis has been linked to fungal infections, further amplifying the appeal of ITZ in this setting.
While there is cautionary advice regarding the possible interference of ITZ with monoclonal antibodies, the overall outlook for Itraconazole as an anti-cancer drug is highly optimistic (12).
In essence, Itraconazole is emerging from its cocoon, transforming from a reliable antifungal into a versatile and promising anti-cancer agent. This evolution bears testimony to the immense potential in the realm of drug repurposing and serves as a beacon of hope for those locked in the fight against cancer, and promising hope to millions worldwide.
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
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.2771