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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Microenvironmental transformations by VEGF- and EGF-receptor inhibition and potential implications for responsiveness to radiotherapy.
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Microenvironmental transformations by VEGF- and EGF-receptor inhibition and potential implications for responsiveness to radiotherapy.

机译：VEGF和EGF受体抑制的微环境转化及其对放射治疗反应的潜在影响。

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摘要

The microregional distribution and dynamics of tumor cell hypoxia and proliferation are important determinants of tumor aggressiveness and resistance to treatment. Modulation of these elements by biological targeted drugs such as EGFR- and VEGFR-inhibitors may improve the effect of radiotherapy significantly. These combinations are being evaluated in clinical trials and evidence of their effectiveness is accumulating. However, the mechanistic basis of this cooperative effect and the role and behavior of the microregional tumor phenotype under EGF- and VEGF-blockage is poorly understood. Unfolding of these interactions and effects further downstream is necessary to exploit these biological modifiers most profitably to unravel questions such as: (1) can microregional phenotypes be modulated by EGFR- or VEGFR-blockage and how do downstream effects in the signaling pathways relate to these changes? (2) How do the microregional changes induced by EGFR- and VEGF-blockage affect the responsiveness of tumors to ionizing radiation? Answering these questions will improve our understanding of tumor growth related phenotypic transformations at the microregional level and how these can be influenced by modulation of the EGF- and VEGF-signaling pathways. This knowledge can be used to identify and improve therapeutic combinations with the novel biological modifiers and test a variety of biological-based treatment approaches.
机译：肿瘤细胞缺氧和增殖的微观区域分布和动力学是决定肿瘤侵袭性和对治疗的抵抗力的重要决定因素。通过生物靶向药物（例如EGFR和VEGFR抑制剂）调节这些元素可能会显着改善放射治疗的效果。这些组合正在临床试验中进行评估，其有效性的证据正在积累。然而，这种协同作用的机制基础以及在EGF和VEGF阻断下微区肿瘤表型的作用和行为知之甚少。为了最有效地利用这些生物修饰剂来揭示以下问题，必须进一步发挥这些相互作用和作用，以解决以下问题：（1）EGFR或VEGFR阻断能否调节微区表型，以及信号通路中的下游效应如何与这些通路相关变化？ （2）EGFR和VEGF阻断引起的微区变化如何影响肿瘤对电离辐射的反应性？回答这些问题将改善我们对微区域水平上与肿瘤生长相关的表型转化的理解，以及如何通过调节EGF和VEGF信号通路来影响这些表型转化。该知识可用于识别和改善与新型生物修饰剂的治疗组合，并测试多种基于生物学的治疗方法。

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