Antipsychotic drugs are primarily known for their role in treating psychotic disorders by modulating dopamine and serotonin receptors. First-generation antipsychotics, such as haloperidol, mainly inhibit D2 dopamine receptors, while second-generation drugs like olanzapine and quetiapine target both dopamine and serotonin pathways. While originally developed for psychiatric conditions, these drugs have shown unexpected potential as anti-cancer agents in pre-clinical studies.

Research has uncovered various mechanisms by which antipsychotics may impact cancer cells. For instance:

• Haloperidol induces apoptosis (programmed cell death), triggers autophagy, and causes cancer cell cycle arrest. It has also demonstrated a synergistic effect when combined with temozolomide, a standard chemotherapy drug for glioblastoma.
• Trifluoperazine enhances radiosensitivity in glioma cells and increases the effectiveness of chemotherapy agents.
• Chlorpromazine has been shown to reduce cancer cell growth and induce cell death in several cancer types, including glioma and leukemia.
• Penfluridol and thioridazine have also exhibited promising anti-cancer properties, with thioridazine even showing success in a clinical trial for acute myeloid leukemia.

Atypical antipsychotics are also being investigated. Olanzapine and quetiapine, for example, have displayed synergistic effects with temozolomide in glioblastoma. Preliminary studies suggest that other second-generation antipsychotics, such as risperidone, aripiprazole, and clozapine, might also have anti-cancer benefits.

While these findings are encouraging, the repurposing of antipsychotics for cancer treatment is not without hurdles. Many of these drugs have significant side effects, including sedation, weight gain, and metabolic disturbances, which could be particularly concerning for cancer patients. Moreover, despite strong pre-clinical evidence, only a handful of early-phase clinical trials have been conducted to date.

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