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Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review

Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recent...

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Autores principales: Nur Husna, Siti Muhamad, Tan, Hern-Tze Tina, Mohamud, Rohimah, Dyhl-Polk, Anne, Wong, Kah Keng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236629/
https://www.ncbi.nlm.nih.gov/pubmed/30542378
http://dx.doi.org/10.1177/1758835918808509
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author Nur Husna, Siti Muhamad
Tan, Hern-Tze Tina
Mohamud, Rohimah
Dyhl-Polk, Anne
Wong, Kah Keng
author_facet Nur Husna, Siti Muhamad
Tan, Hern-Tze Tina
Mohamud, Rohimah
Dyhl-Polk, Anne
Wong, Kah Keng
author_sort Nur Husna, Siti Muhamad
collection PubMed
description Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor.
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spelling pubmed-62366292018-12-10 Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review Nur Husna, Siti Muhamad Tan, Hern-Tze Tina Mohamud, Rohimah Dyhl-Polk, Anne Wong, Kah Keng Ther Adv Med Oncol Review Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor. SAGE Publications 2018-11-09 /pmc/articles/PMC6236629/ /pubmed/30542378 http://dx.doi.org/10.1177/1758835918808509 Text en © The Author(s), 2018 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Nur Husna, Siti Muhamad
Tan, Hern-Tze Tina
Mohamud, Rohimah
Dyhl-Polk, Anne
Wong, Kah Keng
Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review
title Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review
title_full Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review
title_fullStr Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review
title_full_unstemmed Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review
title_short Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review
title_sort inhibitors targeting cdk4/6, parp and pi3k in breast cancer: a review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236629/
https://www.ncbi.nlm.nih.gov/pubmed/30542378
http://dx.doi.org/10.1177/1758835918808509
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