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Cancers 2017, 9(11), 151; https://doi.org/10.3390/cancers9110151

Evolving Therapeutic Strategies to Exploit Chromosome Instability in Cancer

1
Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
2
Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada
*
Author to whom correspondence should be addressed.
Received: 14 October 2017 / Revised: 27 October 2017 / Accepted: 31 October 2017 / Published: 1 November 2017
(This article belongs to the Special Issue Chromosomal Instability and Cancers)
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Abstract

Cancer is a devastating disease that claims over 8 million lives each year. Understanding the molecular etiology of the disease is critical to identify and develop new therapeutic strategies and targets. Chromosome instability (CIN) is an abnormal phenotype, characterized by progressive numerical and/or structural chromosomal changes, which is observed in virtually all cancer types. CIN generates intratumoral heterogeneity, drives cancer development, and promotes metastatic progression, and thus, it is associated with highly aggressive, drug-resistant tumors and poor patient prognosis. As CIN is observed in both primary and metastatic lesions, innovative strategies that exploit CIN may offer therapeutic benefits and better outcomes for cancer patients. Unfortunately, exploiting CIN remains a significant challenge, as the aberrant mechanisms driving CIN and their causative roles in cancer have yet to be fully elucidated. The development and utilization of CIN-exploiting therapies is further complicated by the associated risks for off-target effects and secondary cancers. Accordingly, this review will assess the strengths and limitations of current CIN-exploiting therapies, and discuss emerging strategies designed to overcome these challenges to improve outcomes and survival for patients diagnosed with cancer. View Full-Text
Keywords: chromosome instability; cancer; intratumoral heterogeneity; precision medicine; synthetic lethality; combinatorial chemotherapy chromosome instability; cancer; intratumoral heterogeneity; precision medicine; synthetic lethality; combinatorial chemotherapy
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Thompson, L.L.; Jeusset, L.M.-P.; Lepage, C.C.; McManus, K.J. Evolving Therapeutic Strategies to Exploit Chromosome Instability in Cancer. Cancers 2017, 9, 151.

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