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

Jan A Stratmann, Martin SebastianDepartment of Internal Medicine II, University Clinic of Frankfurt, 60596 Frankfurt, GermanyAbstract: 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 i...

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Autores principales:	Stratmann JA, Sebastian M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	non-small cell lung cancer polo-like kinase targeted therapy therapy resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/de8eaf3055364c7d9ff3222bea2226f1
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spelling	oai:doaj.org-article:de8eaf3055364c7d9ff3222bea2226f12021-12-02T01:02:31ZPolo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers1179-2728https://doaj.org/article/de8eaf3055364c7d9ff3222bea2226f12019-07-01T00:00:00Zhttps://www.dovepress.com/polo-like-kinase-1-inhibition-in-nsclc-mechanism-of-action-and-emergin-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Jan A Stratmann, Martin SebastianDepartment of Internal Medicine II, University Clinic of Frankfurt, 60596 Frankfurt, GermanyAbstract: 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 resistanceStratmann JASebastian MDove Medical Pressarticlenon-small cell lung cancerpolo-like kinasetargeted therapytherapy resistanceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 10, Pp 67-80 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small cell lung cancer polo-like kinase targeted therapy therapy resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	non-small cell lung cancer polo-like kinase targeted therapy therapy resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Stratmann JA Sebastian M Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers
description	Jan A Stratmann, Martin SebastianDepartment of Internal Medicine II, University Clinic of Frankfurt, 60596 Frankfurt, GermanyAbstract: 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
format	article
author	Stratmann JA Sebastian M
author_facet	Stratmann JA Sebastian M
author_sort	Stratmann JA
title	Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers
title_short	Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers
title_full	Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers
title_fullStr	Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers
title_full_unstemmed	Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers
title_sort	polo-like kinase 1 inhibition in nsclc: mechanism of action and emerging predictive biomarkers
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/de8eaf3055364c7d9ff3222bea2226f1
work_keys_str_mv	AT stratmannja pololikekinase1inhibitioninnsclcmechanismofactionandemergingpredictivebiomarkers AT sebastianm pololikekinase1inhibitioninnsclcmechanismofactionandemergingpredictivebiomarkers
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Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers

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