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Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers

Authors Stratmann JA, Sebastian M

Received 16 March 2019

Accepted for publication 24 May 2019

Published 1 July 2019 Volume 2019:10 Pages 67—80


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sai-Hong Ignatius Ou

Jan A Stratmann, Martin Sebastian

Department of Internal Medicine II, University Clinic of Frankfurt, 60596 Frankfurt, Germany

Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Due to often unspecific disease symptoms, locally advanced or metastatic disease is diagnosed in the majority of all cases. Palliative treatment options comprise of conventional cytotoxic agents, immunotherapy with checkpoint inhibitors and the use of specific small-molecule tyrosine kinase inhibitors (TKI). However, these TKIs are mainly restricted to a small proportion of patients with lung cancer that harbor activating driver mutations. Still, the effectiveness and favorable safety profile of these compounds have prompted a systematic search for specific driver mechanisms of tumorigenesis and moreover the development of corresponding kinase inhibitors. In recent years, the Polo-like kinase (PLK) family has emerged as a key regulator in mitotic regulation. Its role in cell proliferation and the frequently observed overexpression in various tumor entities have raised much interest in basic and clinical oncology aiming to attenuate tumor growth by targeting the PLK. In this review, we give a comprehensive summary on the (pre-) clinical development of the different types of PLK inhibitors in lung cancer and summarize their mechanisms of action, safety and efficacy data and give an overview on translational research aiming to identify predictive biomarkers for a rational use of PLK inhibitors.

Keywords: non-small cell lung cancer, Polo-like kinase, targeted therapy, therapy resistance

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