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癌症治疗的分子靶点筛选和鉴定。

Screening and identification of molecular targets for cancer therapy.

机构信息

Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria; Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.

Experimental Orthopaedics, Department of Orthopaedic Surgery, Innsbruck Medical University, Innsbruck, Austria.

出版信息

Cancer Lett. 2017 Feb 28;387:3-9. doi: 10.1016/j.canlet.2016.03.002. Epub 2016 Mar 8.

Abstract

In recent decades, targeted therapeutics have significantly improved therapy results in patients with malignant tumors of different origins. However, malignant diseases characterized by aggressiveness and increased capacity for metastatic spread still require basic researchers and clinicians to direct enormous efforts toward the development of novel therapeutic targets. Potential targets should be selected with the clinical endpoint in view; targeted therapeutics can be developed: for use in combination with currently existing therapeutic approaches in order to improve their efficacy; to overcome the treatment resistance of tumor cells and thus protect the patient from recurrence; to repress molecular mechanisms related to immune escape of cancer cells; and to combat the metastatic dissemination of carcinoma cells. Taking into account the specific clinical aim that should be achieved, different strategies and techniques can be proposed to identify the most promising candidate molecules for further development as therapeutic targets. Since cellular membranes contain a large number of druggable molecules, evaluation of the membrane protein profiles of carcinoma cells having different properties can provide a basis for further development of therapeutic targets. This review considers how cellular membranes obtained from different pre-clinical and clinical samples can be used in screening and to identify targets for cancer therapy.

摘要

近几十年来,针对治疗的药物在治疗不同来源的恶性肿瘤患者方面取得了显著的疗效。然而,具有侵袭性和增加转移扩散能力的恶性疾病仍需要基础研究人员和临床医生投入大量精力来开发新的治疗靶点。选择潜在的靶点时应着眼于临床终点;可以开发针对治疗的药物:与目前现有的治疗方法联合使用,以提高其疗效;克服肿瘤细胞的治疗抵抗,从而保护患者免受复发;抑制与癌细胞免疫逃逸相关的分子机制;以及对抗癌细胞的转移扩散。考虑到应达到的特定临床目标,可以提出不同的策略和技术来确定最有前途的候选分子作为进一步开发的治疗靶点。由于细胞膜包含大量可成药的分子,评估具有不同特性的癌细胞的膜蛋白谱可以为进一步开发治疗靶点提供基础。本综述考虑了如何从不同的临床前和临床样本中获取细胞膜,用于筛选和鉴定癌症治疗的靶点。

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