The role of chromosomal instability in cancer and therapeutic responses
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Villegas Gálvez, Victoria Eugenia
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Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Epidermal Growth Factor Receptor 2 , Estrogen Receptor , Smad2 Protein , Smad4 Protein , Acute Lymphoblastic Leukemia , Aneuploidy , Bladder Cancer , Breast Cancer , Cancer Diagnosis , Cancer Growth , Cancer Prognosis , Cancer Therapy , Chromosomal Instability , Chromosome Aberration , Chromosome Segregation , Colorectal Cancer , Endometrium Cancer , Gene Function , Gene Interaction , Gene Mutation , Genetic Heterogeneity , Genetic Variation , High Hyperdiploid Acute Lymphoblastic Leukemia , Human , Malignant Neoplasm , Multiple Myeloma , Non Recurrent Chromosomal Alteration , Nonhuman , Prostate Cancer , Review , Therapy Resistance , Treatment Outcome , Treatment Response , Tumor Growth , Uterine Cervix Cancer , Factor de Crecimiento Epidérmico Receptor 2 , Receptor de estrógenos , La proteína Smad2 , La proteína smad4