Repurposed Drugs Encyclopedia

Metformin is the world's most prescribed diabetes drug and the most studied repurposed drug in oncology. It activates AMPK, which inhibits mTOR — the master regulator of cell growth and metabolism. Epidemiological studies consistently show diabetic patients on metformin have 20–40% lower cancer incidence and better survival outcomes. Over 100 clinical trials are currently investigating its role in cancer prevention and treatment.

At doses of 1.5–4.5 mg (vs. the standard 50 mg), naltrexone transiently blocks opioid receptors for a few hours each night, causing a rebound overproduction of endogenous opioids (endorphins and met-enkephalin). This pulsed OGF (opioid growth factor) surge modulates the immune system profoundly — boosting NK cell activity, IL-12, and anti-tumour surveillance. Clinical evidence is growing for several cancers, with strongest data in pancreatic cancer and multiple myeloma.

Mebendazole works by binding to beta-tubulin and preventing tubulin polymerisation — the same mechanism many conventional chemotherapy drugs use (taxanes, vinca alkaloids). In cancer research it has shown anti-proliferative, anti-angiogenic, and pro-apoptotic effects across multiple tumour types. A landmark case report documented a patient with Stage 4 non-small cell lung cancer who had a dramatic response after accidentally taking mebendazole. Multiple clinical trials are now underway.

Fenbendazole is a broad-spectrum veterinary anthelmintic in the same benzimidazole class as mebendazole, but with a different pharmacokinetic profile and formulation. It gained significant public attention following the widely shared story of Joe Tippens, an American cancer patient who reported complete remission of Stage 4 small cell lung cancer after taking fenbendazole alongside other supplements. While this is a single anecdotal case, it triggered a surge in preclinical research — primarily from South Korean labs — showing fenbendazole inhibits tubulin polymerisation, stabilises p53 tumour suppressor protein, blocks GLUT glucose transporters (starving cancer cells of sugar), and disrupts cancer cell metabolism. It is chemically closely related to mebendazole but is formulated for animals and has not been studied in formal human clinical trials.

Ivermectin has shown potent anti-cancer activity in multiple preclinical studies, primarily through PAK1 (p21-activated kinase 1) inhibition — a kinase overexpressed in many human cancers including breast, ovarian, and pancreatic tumours. It disrupts multiple oncogenic signalling pathways and selectively induces apoptosis in cancer cells at concentrations achievable with standard dosing. Clinical evidence is at an early stage but growing.

Aspirin is one of the most robustly studied repurposed drugs in cancer prevention. Multiple large prospective cohort studies (including the landmark Nurses' Health Study and ASPREE trial) show regular low-dose aspirin reduces colorectal cancer incidence by 20–40% and may reduce risk of gastric, oesophageal, breast, and ovarian cancers. Its mechanism is primarily COX-2 inhibition, which reduces prostaglandin E2 — a key driver of tumour inflammation, angiogenesis, and immune evasion.

Statins inhibit HMG-CoA reductase — the rate-limiting enzyme of the mevalonate pathway — which is critical not just for cholesterol synthesis but for producing geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP). Cancer cells depend heavily on these molecules to activate Rho and Ras GTPases — key oncogenic drivers. Epidemiological studies show statin users have 10–30% lower risk for several cancers, with strongest evidence in colorectal and breast cancer.

Itraconazole was discovered to have potent anti-cancer activity through a mechanism entirely different from its antifungal properties. It is a powerful inhibitor of the Hedgehog (Hh) signalling pathway — which drives growth of basal cell carcinoma, medulloblastoma, and prostate cancer. Separately, it inhibits angiogenesis by blocking VEGFR2 trafficking and mTOR signalling. Phase II clinical trials have shown significant activity in prostate cancer and basal cell carcinoma.

Doxycycline targets cancer stem cells (CSCs) via a unique mechanism: it inhibits mitochondrial biogenesis and function. Cancer stem cells depend heavily on oxidative phosphorylation (OXPHOS) in their mitochondria, unlike bulk tumour cells which prefer glycolysis. By inhibiting mitochondrial ribosome protein synthesis, doxycycline selectively starves CSCs of energy. It also inhibits matrix metalloproteinases (MMPs) — key enzymes in tumour invasion and metastasis.

Cimetidine has demonstrated anti-cancer effects through a unique immune mechanism: it inhibits ICAM-1 and E-selectin expression on tumour blood vessels. These adhesion molecules are exploited by circulating tumour cells to 'grab' onto vessel walls and form metastases. By blocking this mechanism, cimetidine dramatically reduces metastatic spread in animal models and human studies. Japanese RCTs in colorectal cancer showed significantly improved 10-year survival in patients taking cimetidine perioperatively.

Hydroxychloroquine (HCQ) inhibits autophagy — the process cancer cells use to recycle damaged components and survive under stress (including chemotherapy stress). By raising lysosomal pH, HCQ prevents the final step of autophagy (autolysosome degradation), trapping cancer cells in a pro-death state. It is being extensively tested as a chemotherapy sensitiser — multiple Phase I/II trials show it enhances the efficacy of various cytotoxic agents.

Celecoxib is actually FDA-approved for cancer prevention in Familial Adenomatous Polyposis (FAP) — making it one of the few truly 'approved' repurposed drugs in oncology. It selectively inhibits COX-2, which is overexpressed in many cancers and drives prostaglandin E2 production, fuelling inflammation, angiogenesis, immune evasion, and metastasis. Multiple trials show celecoxib can reduce colorectal polyp recurrence and has activity in breast, prostate, and lung cancers.

Disulfiram's anti-cancer activity was discovered when researchers noticed that alcoholics taking disulfiram had lower cancer rates. Its active metabolite diethyldithiocarbamate (DDC) chelates copper to form DDC-copper complexes that are potently cytotoxic to cancer cells. A landmark 2016 study found that disulfiram-copper destroys the NPL4 protein — which cancer cells need for protein quality control. High-copper tumour environments amplify this effect. Phase II trials are ongoing for GBM and breast cancer.

Niclosamide is emerging as one of the most multi-targeted anti-cancer drugs in the repurposing field. Unlike most drugs which hit one or two pathways, niclosamide simultaneously inhibits Wnt, Notch, STAT3, mTOR, NF-κB, and acts as an oxidative phosphorylation uncoupler — pathways that are often individually responsible for drug resistance, cancer stem cell maintenance, and metastasis. Its main challenge is poor oral bioavailability, which has driven development of nanoparticle formulations.

Dipyridamole inhibits phosphodiesterases and blocks adenosine uptake, elevating extracellular adenosine — which activates A2A receptors on immune cells and creates an immunosuppressive environment that can actually cut both ways in cancer. More interestingly, dipyridamole inhibits thymidylate synthase — the same target as 5-fluorouracil — making it a natural chemosensitiser to 5-FU based regimens. Clinical studies in colorectal and gastric cancer have shown improved outcomes when combined with chemotherapy.