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...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2019-07-01
|
| Series: | Lung Cancer: Targets and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/polo-like-kinase-1-inhibition-in-nsclc-mechanism-of-action-and-emergin-peer-reviewed-article-LCTT |
| _version_ | 1818858138640580608 |
|---|---|
| author | Stratmann JA Sebastian M |
| author_facet | Stratmann JA Sebastian M |
| author_sort | Stratmann JA |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-19T08:51:31Z |
| format | Article |
| id | doaj.art-de8eaf3055364c7d9ff3222bea2226f1 |
| institution | Directory Open Access Journal |
| issn | 1179-2728 |
| language | English |
| last_indexed | 2024-12-19T08:51:31Z |
| publishDate | 2019-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Lung Cancer: Targets and Therapy |
| spelling | doaj.art-de8eaf3055364c7d9ff3222bea2226f12022-12-21T20:28:43ZengDove Medical PressLung Cancer: Targets and Therapy1179-27282019-07-01Volume 10678046716Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkersStratmann JASebastian MJan 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 resistancehttps://www.dovepress.com/polo-like-kinase-1-inhibition-in-nsclc-mechanism-of-action-and-emergin-peer-reviewed-article-LCTTnon-small cell lung cancerpolo-like kinasetargeted therapytherapy resistance |
| spellingShingle | Stratmann JA Sebastian M Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers Lung Cancer: Targets and Therapy non-small cell lung cancer polo-like kinase targeted therapy therapy resistance |
| title | 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_short | 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 |
| topic | non-small cell lung cancer polo-like kinase targeted therapy therapy resistance |
| url | https://www.dovepress.com/polo-like-kinase-1-inhibition-in-nsclc-mechanism-of-action-and-emergin-peer-reviewed-article-LCTT |
| work_keys_str_mv | AT stratmannja pololikekinase1inhibitioninnsclcmechanismofactionandemergingpredictivebiomarkers AT sebastianm pololikekinase1inhibitioninnsclcmechanismofactionandemergingpredictivebiomarkers |