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Targets for improving tumor response to radiotherapy

机译：改善肿瘤对放射疗法反应的靶标

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Radiotherapy is one of the most common treatment modalities for controlling a wide range of tumors. However, it has been shown that radiotherapy alone is unable to completely eradicate some tumors and could be associated with a high possibility of tumor recurrence. To date, various experimental and clinical studies have been conducted to explore some efficient targets within tumor microenvironment (TME) to enhance tumor response to radiotherapy; thus help eliminate or eradicate tumors. Although targeting DNA damage responses (DDRs) is associated with severe toxicities, studies in recent decade suggest that inhibition of some apoptosis/survival targets within TME is promising. This is also associated with changes in the numbers of T regulatory cells (Tregs) and cytotoxic T lymphocytes (CTLs). The inhibition of cyclooxygenase-2 (COX-2), phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) and vascular endothelial growth factor (VEGF) have also shown promising results. The combination of receptor tyrosine kinase (RTK) inhibitors with radiotherapy is interesting as well as the clinical use of some drugs and antibodies. Epidermal growth factor receptor (EGFR) inhibitors are the most common RTK inhibitors. Some clinical trials in recent years have shown very interesting results for immune checkpoint inhibitors (ICIs), especially programmed death-ligand 1 (PD-L1) and CTLs associated antigen 4 (CTLA-4) inhibitors. It has been suggested that administration of ICIs during or after hypofractionated radiotherapy could lead to best results. In this review, we explain TME response to radiotherapy and potential targets for sensitization of cancer cells to radiotherapy.
机译：放射疗法是控制各种肿瘤的最常见的治疗方式之一。然而，已经表明，单独的放疗无法完全消除一些肿瘤，并且可能与肿瘤复发的高可能性相关。迄今为止，已经进行了各种实验和临床研究以探讨肿瘤微环境（TME）内的一些有效靶标，以增强对放射治疗的肿瘤反应;因此，有助于消除或根除肿瘤。虽然靶向DNA损伤反应（DDR）与严重的毒性有关，但近年来的研究表明，抑制TME内的一些凋亡/存活靶标志着。这也与T调节细胞（Tregs）和细胞毒性T淋巴细胞（CTL）的变化有关。还抑制环氧氢止酶-2（COX-2），磷酸膦酸碱基3-激酶（PI3K），哺乳动物靶标的催乳素（MTOR），丝裂原激活的蛋白激酶（MAPK）和血管内皮生长因子（VEGF）的抑制也显示出有前途的结果。受体酪氨酸激酶（RTK）抑制剂的组合具有放射疗法是有趣的以及某些药物和抗体的临床应用。表皮生长因子受体（EGFR）抑制剂是最常见的RTK抑制剂。近年来一些临床试验表明了免疫检查点抑制剂（ICIS），特别是编程的死亡配体1（PD-L1）和CTL相关抗原4（CTLA-4）抑制剂的非常有趣的结果。已经提出，次规的放射治疗期间或之后ICIS给予最佳结果。在本综述中，我们解释了TME对放疗和潜在靶向癌细胞对放射疗法的敏感性的反应。

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