Role of growth factor receptors and their downstream signaling pathways in the resistance or response of rectal adenocarcinoma to neoadjuvant radiochemotherapy

生长因子受体及其下游信号通路在直肠腺癌新辅助放化疗耐药或反应中的作用

• 批准号: 194187606
• 负责人: Professor Dr. Peter Burfeind
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194187606?language=en
• 关键词: Role; growth; factor; receptors; their

Growth factors and their receptors play a significant role in the regulation of cancer growth, tumor angiogenesis, and metastasis, which makes these molecules attractive for targeted therapies. Our recent studies have indicated that the insulin-like growth factor receptor (IGF-IR) together with the epidermal growth factor receptor (EGFR) are able to influence the cellular response of colorectal cancer (CRC) cells. Moreover, inhibition of both receptors has additive effects on proliferation reduction, cell death, and response to 5-fluorouracil (5-FU)-based radiochemotherapy (RCT). From these observations we speculate that the therapeutic efficacy can be even further enhanced by inhibition of more than two receptor tyrosine kinase (RTK) pathways. In this respect, the project aims to identify molecular mechanisms of growth factor receptor cross-talk in rectal adenocarcinomas in response to neoadjuvant therapy. The studies will be performed in established CRC cell lines, primary rectal cancer cell lines, xenotransplants of CRC cell lines, and biopsy material taken from rectal adenocarcinomas. The project will further investigate the mechanisms of resistance to IGF-IR and EGFR inhibitors, thereby identifying new potential therapeutic targets.

生长因子及其受体在调节肿瘤生长、肿瘤血管生成和转移中起重要作用，这使得这些分子对于靶向治疗具有吸引力。我们最近的研究表明，胰岛素样生长因子受体（IGF-IR）与表皮生长因子受体（EGFR）能够影响结直肠癌（CRC）细胞的细胞反应。此外，两种受体的抑制对增殖减少、细胞死亡和对基于5-氟尿嘧啶（5-FU）的放射化疗（RCT）的反应具有累加效应。根据这些观察，我们推测，通过抑制两种以上的受体酪氨酸激酶（RTK）途径，可以进一步增强治疗效果。在这方面，该项目旨在确定直肠腺癌中生长因子受体串扰的分子机制，以响应新辅助治疗。研究将在已建立的CRC细胞系、原代直肠癌细胞系、CRC细胞系的异种移植物和取自直肠腺癌的活检材料中进行。该项目将进一步研究IGF-IR和EGFR抑制剂的耐药机制，从而确定新的潜在治疗靶点。