Repurposing antidepressants for cancer treatment

Cancer is a significant global public health issue, with high incidence and mortality rates. Most current cancer treatments are costly and accompanied by substantial side effects and drug resistance, which necessitating high research costs for developing new therapies. Drug repurposing involves finding novel applications for drugs already approved for clinical use, offering a cost-effective and high-yield approach to cancer treatment. Recent studies have reported that antidepressants, either alone or in combination with other drugs, exhibit inhibitory effects against various types of cancer. In this review, we explore the anticancer potential of antidepressants, including selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, tricyclic/tetracyclic antidepressants, and monoamine oxidase inhibitors. Their antitumor mechanisms encompass promoting apoptosis, inhibiting cell proliferation, mitochondrial-mediated oxidative stress, anti-angiogenesis, immune responses, and lactate dehydrogenase leakage. Combination therapy with antidepressants and conventional antitumor drugs also demonstrates synergistic effects, with advantages such as stronger antitumor activity, fewer side effects, and overcoming to drug resistance. We emphasize the importance of antidepressants in cancer treatment while highlighting current research limitations and future directions.