Thursday, November 24, 2016

Drug Repurposing Strategies in Oncology

Drug Repurposing
Drug repurposing involves the use of existing drugs for new therapeutic purposes but it remains an experimental approach. Always consult a healthcare professional.

Niclosamide: Originally an anti-parasitic, it is repurposed in cancer due to its ability to inhibit the Wnt/Ξ²-catenin pathway, STAT3, and suppress RAS, leading to reduced cancer cell proliferation and increased apoptosis.

Ivermectin: Another anti-parasitic, it has potential anticancer properties by inhibiting tumor growth and reversing drug resistance through pathways like EGFR/ERK/Akt/NF-ΞΊB.

Celecoxib: A nonsteroidal anti-inflammatory drug (NSAID), repurposed for its ability to synergize with other treatments like curcumin, metformin, and aspirin, and to induce apoptosis in cancer cells via COX-2 inhibition.

Phenylbutyrate (Glycerol or Sodium Phenylbutyrate): An HDAC inhibitor and PDK1 inhibitor, it depletes glutamine in cancer cells, induces cellular differentiation, and enhances chemotherapy effectiveness, making it useful against glutamine-addicted cancers.

Aspirin: As an anti-inflammatory drug, it shows potential to reduce cancer growth by targeting inflammation, stimulating T-cell proliferation, and inhibiting metastasis. It is often combined with other drugs like curcumin and atorvastatin for synergistic effects.

Tamoxifen: Primarily a selective estrogen receptor modulator (SERM) for breast cancer, it has also shown efficacy in other cancer types, such as glioma and melanoma. It can synergize with other compounds like melatonin and berberine.

Rapamycin: An mTOR inhibitor, it is used in cancer therapy to prevent cancer cell growth and proliferation, often combined with other strategies for improved efficacy.

Low Dose Naltrexone: Typically an opioid receptor antagonist, at low doses it modulates the immune system and gene expression, potentially slowing cancer progression and improving survival when combined with other therapies like alpha-lipoic acid.

Orlistat: Known for its use in weight loss, it inhibits fatty acid synthase (FASN), which is overexpressed in many cancers. It reduces cancer cell proliferation and induces apoptosis in certain cancers like pancreatic and breast cancer.

Chloroquine: An antimalarial drug, chloroquine is repurposed to inhibit autophagy in cancer cells, enhancing the efficacy of other treatments. It also has synergy with compounds like tetrandrine and honokiol.

Doxycycline: An antibiotic that targets mitochondria, it shows promise in reversing epithelial-to-mesenchymal transition (EMT) and inhibiting metastasis in cancers such as melanoma and lung cancer.

Mebendazole: An antiparasitic, mebendazole has shown antitumor effects by targeting multiple cancer-associated pathways and overcoming drug resistance, particularly in ovarian and thyroid cancers.

Fenbendazole: Another antiparasitic, it has shown anticancer properties, especially when combined with vitamins, by inhibiting tumor growth and enhancing immune cell-mediated tumor killing.

Methylene Blue: Primarily used for its antioxidant properties, it is being explored for its ability to promote mitochondrial function, reduce oxidative stress, and inhibit lactic acid production, which may help in cancer treatment.

Metformin: A diabetes drug, it has shown anticancer effects by activating AMPK, inhibiting mitochondrial respiration, and enhancing the efficacy of other therapies like aspirin. It also limits glucose availability to cancer cells.

Acetazolamide: A carbonic anhydrase inhibitor, it is repurposed to limit tumor growth by reducing pH and affecting tumor metabolism, though it increases ammonia levels and is used in combination with ammonia-lowering agents.

Itraconazole: An antifungal, it is repurposed for its ability to inhibit tumor angiogenesis and target cancer stem cells, especially in melanoma and other solid tumors.

Pantoprazole: A proton pump inhibitor (PPI), it has shown potential in cancer by altering the tumor microenvironment acidity and improving the efficacy of chemotherapy drugs.

Propranolol: A beta-blocker, it is repurposed for cancer treatment due to its ability to inhibit angiogenesis, reduce stress hormones, and target triple-negative breast cancer and colorectal cancer.

Amiloride: Originally a diuretic, it has been repurposed for its role in selectively targeting and killing breast cancer cells through inhibition of cancer cell survival pathways.

Azithromycin: An antibiotic, it inhibits autophagy in cancer cells, making them more susceptible to chemotherapy and radiotherapy, and also reverses drug resistance by targeting P-glycoprotein.