Highlights Thirteen different neoplasms were shown to be susceptible to the antidepressant drug sertraline. The mechanisms of action through which sertraline can kill tumor cells are apoptosis, autophagy, and drug synergism. Sertraline inhibits TCTP, a tumor protein involved in cell survival pathways, responsible for reducing p53 levels. The testing of sertraline in vitro and in vivo resulted in reduced cell counting, shrinking of tumoral masses and increased survival rates. Dose extrapolation from animals to humans has shown a therapeutic index of sertraline that could support future clinical trials.

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