Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

• Published in: Oncogene Vol. 32; no. 46; pp. 5315 - 5330
• Main Authors: Lønning, P E, Knappskog, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.11.2013; Nature Publishing Group
• Subjects: 631/1647/1513/1382; 692/699/67/1059/2326; 692/699/67/68; Antineoplastic Agents - therapeutic use; Apoptosis; Automobile drivers; Cancer; Cell Biology; Chemotherapy; DNA repair; DNA Repair - genetics; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug therapy; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Oncology; Prognosis; review; Norway; chemoresistance; mutations; germline; DNA repair; chemotherapy
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2013.48

Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.