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mTOR与MAPK抑制剂联合使用——治疗肾细胞癌的一种潜在方法。

Combination of mTOR and MAPK Inhibitors-A Potential Way to Treat Renal Cell Carcinoma.

作者信息

Chauhan Ashutosh, Semwal Deepak Kumar, Mishra Satyendra Prasad, Goyal Sandeep, Marathe Rajendra, Semwal Ruchi Badoni

机构信息

Department of Urology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.

Department of Biotechnology, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Harrawala, Dehradun 248001, Uttarakhand, India.

出版信息

Med Sci (Basel). 2016 Oct 17;4(4):16. doi: 10.3390/medsci4040016.

Abstract

Renal cell carcinoma (RCC) is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to understand the biology of RCC. This has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. Patients treated with targeted therapies for RCC had shown positive impact on overall survival, however, no cure is possible and patients need to undergo treatment for long periods of time, which raises challenges to manage the associated adverse events. Moreover, many patients may not respond to it and even response may not last long enough in the responders. Many inhibitors of the Mammalian target of Rapamycin (mTOR) signaling pathway are currently being used in treatment of advanced RCC. Studies showed that inhibitions of mTOR pathways induce Mitogen-Activated Protein Kinase (MAPK) escape cell death and cells become resistant to mTOR inhibitors. Because of this, there is a need to inhibit both pathways with their inhibitors comparatively for a better outcome and treatment of patients with RCC.

摘要

肾细胞癌(RCC)是肾脏中最常见的肿瘤,具有独特的生物学特性,对传统癌症治疗的反应长期不佳。在过去几年中,对RCC生物学的认识有了重大进展。这导致在转移性疾病患者的管理中引入了新型靶向治疗。接受RCC靶向治疗的患者对总生存期有积极影响,然而,无法治愈,患者需要长期接受治疗,这给管理相关不良事件带来了挑战。此外,许多患者可能对此无反应,即使有反应的患者,反应持续时间也可能不够长。目前,许多雷帕霉素哺乳动物靶点(mTOR)信号通路抑制剂正用于治疗晚期RCC。研究表明,抑制mTOR通路会诱导丝裂原活化蛋白激酶(MAPK)逃避细胞死亡,细胞对mTOR抑制剂产生耐药性。因此,需要用抑制剂同时抑制这两条通路,以获得更好的治疗效果并治疗RCC患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d56/5635794/9737f5f3dc0a/medsci-04-00016-g001.jpg

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