Tao Junyan, Sun Dantong, Dong Lina, Zhu Hua, Hou Helei
Precision Medicine Center of Oncology, the Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong 266000 China.
Cancer Cell Int. 2020 Oct 9;20:492. doi: 10.1186/s12935-020-01570-8. eCollection 2020.
The gene encodes neurofibromin, which is one of the primary negative regulatory factors of the Ras protein. Neurofibromin stimulates the GTPase activity of Ras to convert it from an active GTP-bound form to its inactive GDP-bound form through its GTPase activating protein-related domain (GRD). Therefore, neurofibromin serves as a shutdown signal for all vertebrate RAS GTPases. mutations cause a resultant decrease in neurofibromin expression, which has been detected in many human malignancies, including NSCLC, breast cancer and so on. mutations are associated with the underlying mechanisms of treatment resistance discovered in multiple malignancies. This paper reviews the possible mechanisms of mutation-induced therapeutic resistance to chemotherapy, endocrine therapy and targeted therapy in malignancies. Then, we further discuss advancements in targeted therapy for -mutated malignant tumors. In addition, therapies targeting the downstream molecules of might be potential novel strategies for the treatment of advanced malignancies.
该基因编码神经纤维瘤蛋白，它是Ras蛋白的主要负调控因子之一。神经纤维瘤蛋白通过其GTP酶激活蛋白相关结构域（GRD）刺激Ras的GTP酶活性，将其从活性GTP结合形式转化为无活性GDP结合形式。因此，神经纤维瘤蛋白作为所有脊椎动物RAS GTP酶的关闭信号。突变导致神经纤维瘤蛋白表达下降，这在许多人类恶性肿瘤中都有发现，包括非小细胞肺癌、乳腺癌等。突变与多种恶性肿瘤中发现的治疗耐药潜在机制相关。本文综述了突变诱导恶性肿瘤对化疗、内分泌治疗和靶向治疗产生耐药的可能机制。然后，我们进一步讨论针对突变恶性肿瘤的靶向治疗进展。此外，针对下游分子的治疗可能是治疗晚期恶性肿瘤的潜在新策略。
