SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.
SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.
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SHP2：癌症及其微环境界面的多效靶标。
DOI：
10.1158/2159-8290.cd-23-0383
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发表时间：
2023-11-01
期刊：
影响因子：
28.2
通讯作者：
中科院分区：
文献类型：
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作者：
据报道，蛋白磷酸酶SHP2/PTPN11是多种恶性肿瘤中增殖途径的关键调节剂。有趣的是，SHP2也被描述为肿瘤微环境的关键调节因子。基于这一证据，SHP2被认为是癌症中的一个多面靶点，激发了SHP2直接抑制剂的开发将提供肿瘤内在和外在抑制的双重益处的概念。在这篇综述中，我们将讨论SHP2在癌症和肿瘤微环境中的作用，以及利用SHP2抑制剂作为联合药物来提高治疗反应的临床策略。SHP2磷酸酶是一种多效因子，其抑制作用不仅阻碍肿瘤生长，而且重塑肿瘤微环境。虽然它们的单药活性可能有限，但SHP2抑制剂具有成为关键联合药物的潜力，可以增强肿瘤对治疗的反应深度和持久性。
The protein phosphatase SHP2/PTPN11 has been reported to be a key modulator of proliferative pathways in a wide range of malignancies. Intriguingly, SHP2 has also been described as a critical regulator of the tumor microenvironment. Based on this evidence SHP2 is considered a multifaceted target in cancer, spurring the notion that the development of direct inhibitors of SHP2 would provide the twofold benefit of tumor intrinsic and extrinsic inhibition. In this review, we will discuss the role of SHP2 in cancer and the tumor microenvironment, and the clinical strategies in which SHP2 inhibitors are leveraged as combination agents to improve therapeutic response. The SHP2 phosphatase functions as a pleiotropic factor, and its inhibition not only hinders tumor growth but also reshapes the tumor microenvironment. Although their single-agent activity may be limited, SHP2 inhibitors hold the potential of being key combination agents to enhance the depth and the durability of tumor response to therapy.