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Aurora kinase A in gastrointestinal cancers: time to target

Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. During the last two decades, several studies have shown amplification and overexpression of Aurora kinase A (AURKA) in several GI malignancies. These studies demonstrated that AURKA not only plays a role in regulating cell cyc...

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Autores principales: Katsha, Ahmed, Belkhiri, Abbes, Goff, Laura, El-Rifai, Wael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436812/
https://www.ncbi.nlm.nih.gov/pubmed/25987188
http://dx.doi.org/10.1186/s12943-015-0375-4
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author Katsha, Ahmed
Belkhiri, Abbes
Goff, Laura
El-Rifai, Wael
author_facet Katsha, Ahmed
Belkhiri, Abbes
Goff, Laura
El-Rifai, Wael
author_sort Katsha, Ahmed
collection PubMed
description Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. During the last two decades, several studies have shown amplification and overexpression of Aurora kinase A (AURKA) in several GI malignancies. These studies demonstrated that AURKA not only plays a role in regulating cell cycle and mitosis, but also regulates a number of key oncogenic signaling pathways. Although AURKA inhibitors have moved to phase III clinical trials in lymphomas, there has been slower progress in GI cancers and solid tumors. Ongoing clinical trials testing AURKA inhibitors as a single agent or in combination with conventional chemotherapies are expected to provide important clinical information for targeting AURKA in GI cancers. It is, therefore, imperative to consider investigations of molecular determinants of response and resistance to this class of inhibitors. This will improve evaluation of the efficacy of these drugs and establish biomarker based strategies for enrollment into clinical trials, which hold the future direction for personalized cancer therapy. In this review, we will discuss the available data on AURKA in GI cancers. We will also summarize the major AURKA inhibitors that have been developed and tested in pre-clinical and clinical settings.
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spelling pubmed-44368122015-05-20 Aurora kinase A in gastrointestinal cancers: time to target Katsha, Ahmed Belkhiri, Abbes Goff, Laura El-Rifai, Wael Mol Cancer Review Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. During the last two decades, several studies have shown amplification and overexpression of Aurora kinase A (AURKA) in several GI malignancies. These studies demonstrated that AURKA not only plays a role in regulating cell cycle and mitosis, but also regulates a number of key oncogenic signaling pathways. Although AURKA inhibitors have moved to phase III clinical trials in lymphomas, there has been slower progress in GI cancers and solid tumors. Ongoing clinical trials testing AURKA inhibitors as a single agent or in combination with conventional chemotherapies are expected to provide important clinical information for targeting AURKA in GI cancers. It is, therefore, imperative to consider investigations of molecular determinants of response and resistance to this class of inhibitors. This will improve evaluation of the efficacy of these drugs and establish biomarker based strategies for enrollment into clinical trials, which hold the future direction for personalized cancer therapy. In this review, we will discuss the available data on AURKA in GI cancers. We will also summarize the major AURKA inhibitors that have been developed and tested in pre-clinical and clinical settings. BioMed Central 2015-05-20 /pmc/articles/PMC4436812/ /pubmed/25987188 http://dx.doi.org/10.1186/s12943-015-0375-4 Text en © Katsha et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Katsha, Ahmed
Belkhiri, Abbes
Goff, Laura
El-Rifai, Wael
Aurora kinase A in gastrointestinal cancers: time to target
title Aurora kinase A in gastrointestinal cancers: time to target
title_full Aurora kinase A in gastrointestinal cancers: time to target
title_fullStr Aurora kinase A in gastrointestinal cancers: time to target
title_full_unstemmed Aurora kinase A in gastrointestinal cancers: time to target
title_short Aurora kinase A in gastrointestinal cancers: time to target
title_sort aurora kinase a in gastrointestinal cancers: time to target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436812/
https://www.ncbi.nlm.nih.gov/pubmed/25987188
http://dx.doi.org/10.1186/s12943-015-0375-4
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