CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

Jordan L Kohlmeyer; David J Gordon; Munir R Tanas; Varun Monga; Rebecca D Dodd; Dawn E Quelle

doi:10.3390/ijms21083018

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CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

Journal article

Open access

Peer reviewed

CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

Jordan L Kohlmeyer, David J Gordon, Munir R Tanas, Varun Monga, Rebecca D Dodd and Dawn E Quelle

International journal of molecular sciences, Vol.21(8), p.3018

04/24/2020

DOI: 10.3390/ijms21083018

PMCID: PMC7215455

PMID: 32344731

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https://doi.org/10.3390/ijms21083018View

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Abstract

Sarcomas represent one of the most challenging tumor types to treat due to their diverse nature and our incomplete understanding of their underlying biology. Recent work suggests cyclin-dependent kinase (CDK) pathway activation is a powerful driver of sarcomagenesis. CDK proteins participate in numerous cellular processes required for normal cell function, but their dysregulation is a hallmark of many pathologies including cancer. The contributions and significance of aberrant CDK activity to sarcoma development, however, is only partly understood. Here, we describe what is known about CDK-related alterations in the most common subtypes of sarcoma and highlight areas that warrant further investigation. As disruptions in CDK pathways appear in most, if not all, subtypes of sarcoma, we discuss the history and value of pharmacologically targeting CDKs to combat these tumors. The goals of this review are to (1) assess the prevalence and importance of CDK pathway alterations in sarcomas, (2) highlight the gap in knowledge for certain CDKs in these tumors, and (3) provide insight into studies focused on CDK inhibition for sarcoma treatment. Overall, growing evidence demonstrates a crucial role for activated CDKs in sarcoma development and as important targets for sarcoma therapy.

Age Factors

Animals

Antineoplastic Agents - pharmacology

Biomarkers

Cell Cycle - drug effects

Cyclin-Dependent Kinases - antagonists & inhibitors

Cyclin-Dependent Kinases - metabolism

Disease Susceptibility

Gene Expression Regulation, Neoplastic

Humans

Models, Biological

Molecular Targeted Therapy

Protein Kinase Inhibitors - pharmacology

Sarcoma - drug therapy

Sarcoma - etiology

Sarcoma - metabolism

Sarcoma - pathology

Signal Transduction

Transcription, Genetic

Details

Title: Subtitle: CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets
Creators: Jordan L Kohlmeyer - University of Iowa
David J Gordon - University of Iowa
Munir R Tanas - University of Iowa
Varun Monga - University of Iowa
Rebecca D Dodd - University of Iowa
Dawn E Quelle - University of Iowa
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.21(8), p.3018
DOI: 10.3390/ijms21083018
PMID: 32344731
PMCID: PMC7215455
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Grant note: T32 GM067795 / NIGMS NIH HHS 2019 Young Investigator Award / Children's Tumor Foundation P30 CA086862 / NCI NIH HHS Mezhir Research Award / Holden Comprehensive Cancer Center, University of Iowa P50 CA174521 / NCI NIH HHS
Language: English
Date published: 04/24/2020
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Hematology/Oncology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984186518902771

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