Microtubule-targeting agents in the treatment of non-small cell lung cancer: insights on new combination strategies and investigational compounds

Abstract

ABSTRACT Introduction: The management of non-small cell lung cancer (NSCLC) has been substantially improved in the last few years; it has been revolutionized by a patient-tailored approach, especially in the oncogene addicted disease, and by novel combinations containing immune checkpoint inhibitors. However, chemotherapy still represents a mainstay that persists over the decades with limited novelties. Tubulin inhibitors belong to different sub-classes of drugs that share the capability to interfere with mitosis by a direct action on the microtubule system. Among them, taxanes and vinca alkaloids still have a prominent role in clinical practice. Areas covered: This review summarizes the mechanisms of action, current role and future directions of microtubule targeting agents; we focus on investigational agents in phase I and II clinical trials. Expert opinion: Chemotherapy maintains a pivotal role in the treatment of NSCLC. New generation agents that have the potential to overcome the mechanisms of resistance to the available drugs may provide new therapeutic opportunities. Predictive biomarkers derived from combination strategies and phase III studies are necessary going forward. Trial registration: ClinicalTrials.gov identifier: NCT02309177. Trial registration: ClinicalTrials.gov identifier: NCT02014337. Trial registration: ClinicalTrials.gov identifier: NCT03102606. Trial registration: EU Clinical Trials Register identifier: 021855-15. Trial registration: ClinicalTrials.gov identifier: NCT01454934. Trial registration: ClinicalTrials.gov identifier: NCT00651508. Trial registration: ClinicalTrials.gov identifier: NCT02812667. Trial registration: ClinicalTrials.gov identifier: NCT02846792. Trial registration: ClinicalTrials.gov identifier: NCT02533674.