title: Regulation of therapeutic resistance in cancers by receptor tyrosine kinases.
abstract: In response to DNA damage lesions due to cellular stress, DNA damage response (DDR) pathways are activated to promote cell survival and genetic stability or unrepaired lesion-induced cell death. Current cancer treatments predominantly utilize DNA damaging agents, such as irradiation and chemotherapy drugs, to inhibit cancer cell proliferation and induce cell death through the activation of DDR. However, a portion of cancer patients is reported to develop therapeutic resistance to these DDR-inducing agents. One significant resistance mechanism in cancer cells is oncogenic kinase overexpression, which promotes cell survival by enhancing DNA damage repair pathways and evading cell cycle arrest. Among the oncogenic kinases, overexpression of receptor tyrosine kinases (RTKs) is reported in many of solid tumors, and numerous clinical trials targeting RTKs are currently in progress. As the emerging trend in cancer treatment combines DNA damaging agents and RTK inhibitors, it is important to understand the substrates of RTKs relative to the DDR pathways. In addition, alteration of RTK expression and their phosphorylated substrates can serve as biomarkers to stratify patients for combination therapies. In this review, we summarize the deleterious effects of RTKs on the DDR pathways and the emerging biomarkers for personalized therapy.
authors.affiliation: Graduate School of Biomedical Science, The University of Texas Health Science Center at HoustonHouston, Texas 77030, USA; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer CenterHouston, Texas, 77030, USA.
authors.forename: Mei-Kuang
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Graduate School of Biomedical Science, The University of Texas Health Science Center at HoustonHouston, Texas 77030, USA; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer CenterHouston, Texas, 77030, USA; Center of Molecular Medicine and Graduate Institute of Cancer Biology, China Medical UniversityTaichung 404, Taiwan; Department of Biotechnology, Asia UniversityTaichung 413, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
keywords: DNA damage; DNA repair; Receptor tyrosine kinase; epidermal growth factor receptor; signaling