everolimus + topotecan

A combination therapy comprising the mTOR inhibitor everolimus (RAD001) and the topoisomerase I inhibitor topotecan, specifically investigated for the treatment of advanced or recurrent endometrial cancer. Everolimus is a rapamycin analog that binds to the intracellular protein FKBP-12, forming a complex that inhibits the mammalian target of rapamycin complex 1 (mTORC1). This inhibition leads to a reduction in protein synthesis, cell cycle progression, and angiogenesis, which are often dysregulated in endometrial malignancies. Topotecan is a semi-synthetic derivative of camptothecin that acts as a cytotoxic chemotherapy agent by stabilizing the covalent complex between DNA and the topoisomerase I enzyme. This stabilization prevents the religation of DNA strands, resulting in lethal double-strand breaks during the S-phase of the cell cycle. The combination was evaluated in a Phase I dose-escalation study led by Yale University to determine the safety and synergistic potential of these two oral agents in patients with refractory gynecological cancers.

Brand names

AfinitorHycamtin

Other names

RAD001 + topotecaneverolimus and topotecan