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Azacitidine + nab-paclitaxel is a combination therapy comprising **azacitidine**, a nucleoside analog and DNA methyltransferase inhibitor, and **nab-paclitaxel**, a nanoparticle albumin-bound formulation of the antimicrotubule agent paclitaxel. Azacitidine incorporates into DNA and inhibits DNA methyltransferases, resulting in hypomethylation of DNA and reactivation of silenced tumor suppressor genes. This can upregulate the SPARC protein in tumors, potentially enhancing the accumulation of albumin-bound drugs such as nab-paclitaxel at the tumor site[1][3][5]. Nab-paclitaxel, on the other hand, stabilizes microtubules, inhibits their disassembly, and interferes with mitotic and interphase functions of tumor cells[2][4][6]. The combination has shown promising clinical activity in phase I trials in patients with advanced cancers, including ovarian, endometrial, lung, sarcoma, pancreatic, breast cancer, and diffuse large B-cell lymphoma, with complete and partial responses observed[1][3][5]. The rationale for the combination includes the proposed synergy of priming tumors with azacitidine to upregulate SPARC and potentiate the tumor delivery of nab-paclitaxel[3].
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