gemcitabine + plitidepsin

Gemcitabine + plitidepsin is a combination of two anticancer agents used in investigational settings for the treatment of various solid tumors and hematological malignancies. Gemcitabine is a nucleoside analog that inhibits DNA synthesis, leading to cell death. Plitidepsin is a cyclic depsipeptide originally isolated from the Mediterranean tunicate Aplidium albicans and now produced synthetically; it exerts its antitumor effects primarily by inhibiting eukaryotic elongation factor 1 alpha 2 (eEF1A2), resulting in disruption of protein synthesis, induction of oxidative stress, activation of apoptotic pathways (including JNK and p38 MAPK), and inhibition of angiogenesis via suppression of VEGF secretion. Preclinical studies have shown synergistic antitumor activity when these drugs are combined, particularly in pancreatic cancer models[1][3]. The combination has been evaluated in early-phase clinical trials for safety and efficacy[2].