LY2523355 + granulocyte colony-stimulating factor

LY2523355 + granulocyte colony-stimulating factor is a combination therapy used in oncology trials for advanced solid tumors. LY2523355 (litronesib) is a small molecule allosteric inhibitor of the mitotic kinesin Eg5 (also known as KIF11 or kinesin spindle protein-5), essential for bipolar mitotic spindle formation. Inhibition of Eg5 results in mitotic arrest and apoptosis of proliferating tumor cells. Granulocyte colony-stimulating factor (G-CSF), such as filgrastim or pegfilgrastim, is routinely co-administered to reduce the risk and severity of neutropenia—a dose-limiting toxicity of LY2523355—by stimulating proliferation and differentiation of neutrophil precursors. This combination has been explored in phase 1 and phase 2 studies for various advanced or metastatic solid tumors, including breast, ovarian, colorectal, lung, esophageal, prostate, and head and neck cancers. No objective tumor responses have been observed, but the combination is used to optimize tolerability and manage hematologic toxicities[1][2][3][5][7].