Abstract
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.
Highlights
Cancer is a multifactorial disease, which is characterized by the presence of a population of cells with complex and heterogeneous karyotypes [1]
The analysis of these results suggests a possible explanation of how exacerbated chromosome instability (CIN) could be operating against the tumor: too much CIN leads to excessive mutations that result in the loss of benefits that the cells had initially acquired toward their tumor transformation [146,147]
The tumor-promoting role of CIN has been widely reported in several neoplasms; our understanding of CIN has increased in last years, it is still necessary to consider its consequences in the context of cancer as a heterogeneous and complex disease, instead of one in which
Summary
Cancer is a multifactorial disease, which is characterized by the presence of a population of cells with complex and heterogeneous karyotypes [1]. Tumor size, histological grade, histotype and immunohistochemical results of prognostic factors play major roles in planning therapeutic strategies [2] (e.g., targeted therapy or chemotherapy). This has been a successful approach, many patients relapse and/or eventually develop resistance. CIN has been recognized as a source of genetic variation, favoring tumor adaptations to stressful environments and cytotoxic anticancer drugs [3] CIN has has been with cancer cancer therapy, therapy, contradictory have been reported regarding its implications for the therapeutic response [4,5,6] It is necessary have been reported regarding its implications for the therapeutic response [4,5,6].
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