Anticancer Mechanisms

Itraconazole is being repurposed in oncology because it appears to act on multiple cancer-relevant pathways beyond its original antifungal use.

Primary mechanisms

1. Hedgehog pathway inhibition

• one of itraconazole's best-known repurposing mechanisms

• relevant in cancers driven by aberrant Hedgehog signalling

2. Angiogenesis inhibition

• suppresses VEGFR2-related signalling

• reduces tumour microvessel density

• limits tumour blood-vessel growth

3. AKT / mTOR pathway inhibition

• interferes with tumour survival and growth signalling

• relevant in resistant and aggressive tumour biology

4. Wnt / β-catenin pathway modulation

• affects stem-like and proliferative signalling

• supports its broader anti-survival profile

5. Tubulin- and proliferation-related disruption

• in some models, the broader impact on proliferation and division adds to the anti-tumour effect

6. Multidrug-resistance reversal

• may interfere with drug-resistance systems that help tumour cells survive standard treatment

Practical interpretation

Itraconazole is especially interesting because it hits several pathways that matter in resistant or angiogenesis-heavy cancers, which is why it continues to attract attention as a repurposed adjunct.

Key References

Repurposing itraconazole for the treatment of cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC6769799/

Repurposed itraconazole for use in the treatment of malignancies as a promising therapeutic strategy
https://www.sciencedirect.com/science/article/abs/pii/S1043661821003328

Discovery of novel VEGFR-2 inhibitors from mebendazole
https://papers.ssrn.com/sol3/Delivery.cfm/3e62d80d-126c-4f09-a324-f81ec7aeae21-MECA.pdf?abstractid=5314948&mirid=1