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nab-sirolimus + gemcitabine is an investigational combination therapy consisting of **nab-sirolimus**, a nanoparticle albumin-bound formulation of the mTOR inhibitor sirolimus, and **gemcitabine**, a nucleoside analog cytotoxic chemotherapy agent. The combination aims to exploit synergistic antitumor effects, particularly in sarcomas with TSC1 or TSC2 loss-of-function mutations. Nab-sirolimus inhibits the mammalian target of rapamycin (mTOR) pathway, which is frequently hyperactivated in TSC-mutant tumors, while gemcitabine interferes with DNA synthesis, leading to cytotoxicity. The combination is being studied primarily in advanced leiomyosarcomas and soft tissue sarcomas, especially those bearing TSC mutations, and is undergoing Phase I clinical evaluation to determine safety, tolerability, efficacy, and recommended dosing[1][3][5][7].
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