期刊
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
卷 1868, 期 1, 页码 69-92出版社
ELSEVIER
DOI: 10.1016/j.bbcan.2017.02.003
关键词
-
资金
- National Institutes of Health [P50 CA 127297, RO1 CA195586, RO1 CA 206444, UO1 CA 185148, EDRN UO1 CA200466]
Despite recent advances in radiotherapy, a majority of patients diagnosed with pancreatic cancer (PC) do not achieve objective responses due to the existence of intrinsic and acquired radioresistance. Identification of molecular mechanisms that compromise the efficacy of radiation therapy and targeting these pathways is paramount for improving radiation response in PC patients. In this review, we have summarized molecular mechanisms associated with the radio-resistant phenotype of PC. Briefly, we discuss the reversible and irreversible biological consequences of radiotherapy, such as DNA damage and DNA repair, mechanisms of cancer cell survival and radiation-induced apoptosis following radiotherapy. We further describe various small molecule inhibitors and molecular targeting agents currently being tested in preclinical and clinical studies as potential radiosensitizers for PC. Notably, we draw attention towards the confounding effects of cancer stem cells, immune system, and the tumor microenvironment in the context of PC radioresistance and radiosensitization. Finally, we discuss the need for examining selective radioprotectors in light of the emerging evidence on radiation toxicity to non-target tissue associated with PC radiotherapy. (C) 2017 Elsevier B.V. All rights reserved.
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