Department of Medicine, University of Lausanne, Lausanne, Switzerland.
Clin Cancer Res. 2012 Oct 1;18(19):5196-202. doi: 10.1158/1078-0432.CCR-11-1758. Epub 2012 Jun 22.
Radiotherapy is a well-established therapeutic modality in oncology. It provides survival benefits in several different cancer types. However, cancers relapsing after radiotherapy often develop into more aggressive conditions that are difficult to treat and are associated with poor prognosis. Cumulative experimental evidence indicates that the irradiated tumor bed contributes to such aggressive behavior. The involved mechanisms have for long remained elusive. Recent progress in the field revealed previously unrecognized cellular and molecular events promoting growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Cellular mechanisms include inhibition of sprouting angiogenesis, formation of hypoxia, activation and differentiation of stromal cells, and recruitment of bone marrow-derived cells with vasculogenic and prometastatic activities. Identified pathways include TGF-β/ALK5, CXCL12/CXCR4, KITL/KIT, and CYR61/αVβ5 integrin. The availability of pharmacologic inhibitors impinging on these pathways opens novel opportunities for translational and clinical studies. These experimental results and ongoing work highlight the importance of the irradiated microenvironment in modulating the tumor response to radiotherapy and open new opportunities for the development of novel therapeutic strategies for patients with cancer who relapse after radiotherapy. Here, we review and discuss recent advances in the field and their translational and therapeutic implications to human cancer treatment.
放射治疗是肿瘤学中一种成熟的治疗方式。它为多种不同类型的癌症提供了生存益处。然而，放射治疗后复发的癌症常常发展成更具侵袭性的疾病，难以治疗且预后不良。累积的实验证据表明，放射治疗后的肿瘤床有助于这种侵袭性行为。相关机制长期以来一直难以捉摸。该领域的最新进展揭示了以前未被识别的促进肿瘤在放射微环境中生长、侵袭和转移的细胞和分子事件。细胞机制包括抑制发芽血管生成、形成缺氧、激活和分化基质细胞，以及招募具有血管生成和促转移活性的骨髓来源细胞。已确定的途径包括 TGF-β/ALK5、CXCL12/CXCR4、KITL/KIT 和 CYR61/αVβ5 整联蛋白。针对这些途径的药理学抑制剂的出现为转化和临床研究开辟了新的机会。这些实验结果和正在进行的工作强调了放射微环境在调节肿瘤对放射治疗的反应中的重要性，并为放射治疗后复发的癌症患者开发新的治疗策略提供了新的机会。在这里，我们回顾和讨论该领域的最新进展及其对人类癌症治疗的转化和治疗意义。
