Biological determinants of radioresistance and their remediation in pancreatic cancer.
Biological determinants of radioresistance and their remediation in pancreatic cancer.
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DOI：
10.1016/j.bbcan.2017.02.003
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Batra SK
中科院分区：
文献类型：
--
作者：
Seshacharyulu P;Baine MJ;Souchek JJ;Menning M;Kaur S;Yan Y;Ouellette MM;Jain M;Lin C;Batra SK
尽管放射治疗最近取得了进展，但由于内在和获得性放射抗性的存在，大多数诊断为胰腺癌（PC）的患者并未获得客观缓解。识别损害放射治疗疗效的分子机制并针对这些途径对于改善 PC 患者的放射反应至关重要。在这篇综述中，我们总结了与 PC 放射抗性表型相关的分子机制。简而言之，我们讨论了放射治疗的可逆和不可逆生物学后果，例如 DNA 损伤和 DNA 修复、癌细胞存活机制和放射治疗后辐射诱导的细胞凋亡。我们进一步描述了目前正在临床前和临床研究中测试的各种小分子抑制剂和分子靶向剂作为 PC 的潜在放射增敏剂。值得注意的是，我们提请人们注意癌症干细胞、免疫系统和肿瘤微环境在 PC 放射抗性和放射增敏背景下的混杂影响。最后，我们讨论了根据与 PC 放疗相关的非靶组织辐射毒性的新证据，检查选择性放射防护剂的必要性。
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.
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影响因子：
45.3
作者：
Brizel, DM;Wasserman, TH;Sauer, R
通讯作者：
Sauer, R
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK
DOI：
10.4297/najms.2011.31
发表时间：
2011-01
期刊：
North American journal of medical sciences
影响因子：
--
作者：
Andrén-Sandberg A
通讯作者：
Andrén-Sandberg A
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
8
作者：
Bockbrader, KM;Tan, MJ;Sun, Y
通讯作者：
Sun, Y