Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer

Expert Opin Pharmacother. 2017 May;18(7):701-716. doi: 10.1080/14656566.2017.1316374. Epub 2017 Apr 17.

Abstract

Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during their treatment course. Either used alone or in combination, tubulin inhibitors have demonstrated clinical benefits in different settings of lung cancer management. Areas covered: This review first discusses FDA-approved tubulin inhibitors for NSCLC, such as paclitaxel, docetaxel, vinorelbine, and nab-paclitaxel. The article then provides a summary of novel tubulin inhibitors, including cabazitaxel, eribulin, ixabepilone, patupilone, plinabulin, new colchicine analogues and others. It also discusses new tubulin inhibitor combinations with immunotherapy (PD-1/PD-L1 inhibitors) and molecularly-targeted therapies (e.g. anti-angiogenic agents, mTOR inhibitors, heat shock protein 90 inhibitors, MEK inhibitors, and anti-HER3 agents). Lastly, emerging data on potential resistance mechanisms and predictive biomarkers for tubulin inhibitors are explored. Expert opinion: Tubulin inhibitors will likely continue to play important roles in NSCLC management due to the advent of novel agents and combinations. Through further understanding of tumor biology, investigation of drug resistance, and development of predictive biomarkers, we will be better positioned to incorporate microtubule inhibition into patient specific treatment strategies.

Keywords: Adenocarcinoma; NSCLC; docetaxel; microtubule; novel; paclitaxel; squamous cell; tubulin; tubulin inhibitor; vinorelbine.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • Humans
  • Lung Neoplasms / drug therapy*
  • Tubulin Modulators / therapeutic use*

Substances

  • Antineoplastic Agents
  • HSP90 Heat-Shock Proteins
  • Tubulin Modulators