EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection.
EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection.
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DOI：
10.1016/j.pharmthera.2015.07.002
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发表时间：
2015-10
影响因子：
13.5
通讯作者：
Lawrence TS
中科院分区：
文献类型：
--
作者：
Cuneo KC;Nyati MK;Ray D;Lawrence TS
表皮生长因子受体（EGFR）在许多类型的恶性肿瘤（包括头颈癌、结直肠癌和非小细胞肺癌）的肿瘤进展和治疗耐药性中起重要作用。几种EGFR靶向治疗作为单药或与化疗联合使用是有效的。鉴于与放化疗相关的毒性和在几种类型的癌症中观察到的不良结果，EGFR靶向药物与或不与化疗的组合已经在接受放疗的患者中进行了测试。迄今为止，FDA批准的抗EGFR疗法与放射疗法组合的唯一用途是用于局部晚期头颈癌。考虑到EGFR在肺癌和结直肠癌中的重要作用以及EGFR抑制与化疗联合治疗在这些疾病部位的益处，令人困惑的是，EGFR靶向治疗与放疗或放化疗联合治疗为什么没有更成功。本文就EGFR靶向治疗联合放化疗的临床研究进展进行综述。我们讨论了EGFR与辐射的相互作用，包括辐射诱导的EGFR信号转导，EGFR对DNA损伤修复的影响，以及辐射增敏的可能机制。最后，我们研究了计划EGFR靶向治疗与放化疗和使用预测性生物标志物来改善患者选择的潜在陷阱。
The epidermal growth factor receptor (EGFR) plays an important role in tumor progression and treatment resistance for many types of malignancies including head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted therapies are efficacious as single agents or in combination with chemotherapy. Given the toxicity associated with chemoradiation and poor outcomes seen in several types of cancers, combinations of EGFR targeted agents with or without chemotherapy have been tested in patients receiving radiation. To date, the only FDA approved use of an anti-EGFR therapy in combination with radiation therapy is for locally advanced head and neck cancer. Given the important role EGFR plays in lung and colorectal cancer and the benefit of EGFR inhibition combined with chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies in combination with radiation or chemoradiation have not been more successful. In this review we summarize the clinical findings of EGFR targeted therapies combined with radiation and chemoradiation regimens. We then discuss the interaction between EGFR and radiation including radiation induced EGFR signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of radiosensitization. Finally, we examine the potential pitfalls with scheduling EGFR targeted therapies with chemoradiation and the use of predictive biomarkers to improve patient selection.