An update on the developing mitotic inhibitors for the treatment of non-small cell carcinoma

Expert Opin Emerg Drugs. 2017 Sep;22(3):213-222. doi: 10.1080/14728214.2017.1369952.

Abstract

Mitosis is necessary to sustain life and is followed immediately by cell division into two daughter cells. Microtubules play a key role in the formation of the mitotic spindle apparatus and cytokinesis at the end of mitosis. Various anti-microtubule agents such as taxanes and vinca alkaloids are widely used in the treatment of advanced non-small cell lung cancer (NSCLC) but their use is associated with hematologic toxicity profile, acquired resistance and hypersensitivity reactions. Areas covered: The Nab-paclitaxels are the more recent antimitotic agents approved in NSCLC showing a better tolerability and activity when compared to previous ones. Despite this, the outcome of patients with advanced non-small cell lung cancer is poor. Due to the key role of mitosis, research is focused on the identification of new mitotic drug targets other than microtubule inhibitors, such as cell cycle targets, aurora kinases and Polo-like kinases. Expert opinion: Despite improvements in chemotherapeutic choices and supportive care, the majority of patients experience a deteriorating quality of life and significant toxicities associated to a poor outcome. Thus, the therapeutic management of patients with advanced NSCLC represents an ongoing challenge and novel agents targeting mitosis are under investigation.

Keywords: Mitosis; NSCLC; anti-mitrotubule agents; aurora kinase; cycle cellular targets; nab-paclitaxel.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimitotic Agents / adverse effects
  • Antimitotic Agents / pharmacology
  • Antimitotic Agents / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Design
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mitosis
  • Molecular Targeted Therapy
  • Quality of Life

Substances

  • Antimitotic Agents
  • Antineoplastic Agents