Emerging mitotic inhibitors for non-small cell carcinoma

Abstract

Introduction: Mitosis is the key event of the cell cycle, and microtubules play an important part in an array of cellular functions besides mitosis, including maintenance of cell shape, cell locomotion, and the movement of intracellular organelles. Various anti-microtubule agents interfere with normal progression of mitosis, such as taxanes and vinca alkaloids. These compounds are widely used in the treatment of advanced non-small cell lung cancer (NSCLC), but their use has been limited by toxicity profile (hematologic and not), acquired resistance, and hypersensitivity reactions.

Areas covered: Recently innovative drug carrier such as nanoparticle showed to reduce toxicity and improve drugs' efficacy. Nanoparticle albumin-bound (nab)-paclitaxel has been recently approved for the use in breast and NSCLC with very promising results in pancreatic adenocarcinoma. Furthermore, the identification of novel mitotic drug targets other than microtubules has gained recently much attention, such as aurora kinases, Polo-like kinase1 (PLK1), kinesin spindle protein (KSP), and centromeric protein E (CENPE).

Expert opinion: Despite recent advances in treatment, NSCLC continues to be the leading cause of cancer death worldwide. Novel agents that target the spindle microtubule elements of mitosis, as well as those that target the non-microtubule effectors of mitosis, are under investigation.

Keywords::

• anti-microtubule agents
• aurora kinases
• epothilones
• eribulin
• KEP
• mitosis
• nab-paclitaxel
• polo-like kinase