Dr. Weeks’ Comment: All treatment decisions require a risk/benefit assessment. Wise and compassionate doctors remember that the first rule of medicine is “First Do No Harm”. In that ironic light, we all acknowledge that the standard of care for cancer (chemotherapy, radiation therapy, surgery) has been universally disappointing. Now we learn about repurposed drugs which seem to have powerful, anti-cancer benefits with very low risk of negative side-effects. If curious, read the following and share this info about a commonly used antifungal drug itraconazole (Sporanox) with your oncologist.
Itraconazole and Cancer Therapy
Itraconazole, an FDA-approved antifungal medication, has been repurposed as a potential anti-cancer agent. Its anti-cancer effects have been demonstrated in various cancer types, including glioblastoma, basal cell carcinoma, non-small cell lung cancer (NSCLC), epithelial ovarian cancer, and colon cancer.
Mechanisms of Action
Itraconazole’s anti-cancer effects are attributed to its ability to:
- Inhibit the Hedgehog pathway, a key signaling pathway involved in cancer development and progression
- Induce autophagic cell death, a process by which cancer cells self-digest and eliminate damaged cellular components
- Inhibit transketolase expression, a key enzyme involved in cancer cell metabolism
- Synergize with other drugs to enhance anti-cancer effects
Clinical Trials and Evidence
Clinical trials have shown that itraconazole treatment benefits patients with prostate, lung, and basal cell carcinoma. Additionally, there are reports of activity in leukemia, ovarian, breast, and pancreatic cancers.
Dose-Response Correlation
A study found a significant correlation between the levels of itraconazole in the body and its ability to shrink tumors. The optimal dose range for anti-cancer effects appears to be between 200-600 milligrams per day, with a steady dose of 300 milligrams twice a day with food showing promising results.
Cancer in General
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588108/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406527/
https://www.sciencedirect.com/science/article/pii/S0753332222010058
https://pubmed.ncbi.nlm.nih.gov/36055112/
Prostate Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579600/
https://www.sciencedirect.com/science/article/abs/pii/S1558767313002863
Pancreatic Cancer
https://ar.iiarjournals.org/content/35/7/4191
https://pubmed.ncbi.nlm.nih.gov/29484419/
Squamous cell Carcinoma
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.828983/full
Endometrial Cancer
https://pubmed.ncbi.nlm.nih.gov/26722038/
Ovarian Cancer
https://www.nature.com/articles/s41598-017-06510-7
Non- Small Cell Lung Cancer
https://clinicaltrials.gov/study/NCT03664115
https://pubmed.ncbi.nlm.nih.gov/32847935/
Colorectal Cancer
https://pubmed.ncbi.nlm.nih.gov/38278779/
Liver Cancer
https://pubmed.ncbi.nlm.nih.gov/32942154/
Bladder Cancer
https://pubmed.ncbi.nlm.nih.gov/26812305/
Gastric Cancer
https://jeccr.biomedcentral.com/articles/10.1186/s13046-017-0526-0
Breast Cancer
Itraconazole and Breast Cancer
Itraconazole, an antifungal medication, has been repurposed as a potential anticancer agent, including its application in breast cancer treatment. Here are key findings and mechanisms:
- Reversing chemoresistance: Itraconazole has been shown to reverse chemoresistance mediated by P-glycoprotein (P-gp) in breast cancer cells, making chemotherapy more effective (Table I).
- Inhibiting Hedgehog signaling: Itraconazole inhibits Hedgehog signaling, a key pathway in breast cancer stem cells, leading to reduced tumor growth and increased apoptosis (cell death) (9, 14-17).
- Autophagic cell death: Itraconazole induces autophagic cell death in breast cancer cells, contributing to its anticancer activity (12, 17).
- Combination therapy: Itraconazole has been combined with chemotherapy (docetaxel, carboplatin, and gemcitabine) in clinical trials, demonstrating promising results in heavily pre-treated patients with triple-negative breast cancer (TNBC) (33).
- Clinical trials: Studies have reported activity in breast cancer, including TNBC, as well as in other cancer types, such as prostate, lung, basal cell carcinoma, leukaemia, ovarian, and pancreatic cancers (16, 25, 27, 30, 35).
Mechanisms of action:
- Inhibition of P-gp-mediated multidrug resistance
- Inhibition of Hedgehog signaling
- Induction of autophagic cell death
- Inhibition of angiogenesis and lymphangiogenesis
- Interference with cancer-stromal cell interactions
Clinical evidence:
- A pilot trial of itraconazole pharmacokinetics in patients with metastatic breast cancer showed correlations between plasma levels and measures of angiogenesis (34).
- A case report described a patient with pancreatic adenocarcinoma who responded to itraconazole treatment (35).
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