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Gemcitabine + sunitinib is a combination therapy consisting of gemcitabine, a nucleoside analog, and sunitinib, a multi-targeted receptor tyrosine kinase inhibitor. Gemcitabine works by inhibiting DNA synthesis and promoting apoptosis in malignant cells undergoing DNA synthesis. It is phosphorylated to active metabolites that compete with deoxycytidine triphosphate for incorporation into DNA, leading to chain termination and cell death. It also inhibits Ribonucleoside-diphosphate reductase large subunit and subunit M2, and UMP-CMP kinase. Sunitinib inhibits multiple receptor tyrosine kinases including VEGFR-1,-2,-3, PDGFR-α,-β, KIT, RET, CSF-1R, and FLT3, affecting both tumor angiogenesis and direct tumor cell growth. The combination has shown additive effects in inhibiting cell proliferation and inducing apoptosis in preclinical studies.
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