Martin-Liberal J, Cameron A J, Claus J, Judson I R, Parker P J, Linch M
Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Biochim Biophys Acta. 2014 Dec;1846(2):547-59. doi: 10.1016/j.bbcan.2014.10.002. Epub 2014 Oct 16.
Protein kinase C (PKC) is a family of serine/threonine tyrosine kinases that regulate many cellular processes including division, proliferation, survival, anoikis and polarity. PKC is abundant in many human cancers and aberrant PKC signalling has been demonstrated in cancer models. On this basis, PKC has become an attractive target for small molecule inhibition within oncology drug development programmes. Sarcoma is a heterogeneous group of mesenchymal malignancies. Due to their relative insensitivity to conventional chemotherapies and the increasing recognition of the driving molecular events of sarcomagenesis, sarcoma provides an excellent platform to test novel therapeutics. In this review we provide a structure-function overview of the PKC family, the rationale for targeting these kinases in sarcoma and the state of play with regard to PKC inhibition in the clinic.
蛋白激酶C（PKC）是一类丝氨酸/苏氨酸酪氨酸激酶家族，可调节许多细胞过程，包括分裂、增殖、存活、失巢凋亡和极性。PKC在许多人类癌症中大量存在，并且在癌症模型中已证实PKC信号异常。在此基础上，PKC已成为肿瘤学药物开发计划中极具吸引力的小分子抑制靶点。肉瘤是间充质恶性肿瘤的异质性群体。由于它们对传统化疗相对不敏感，以及对肉瘤发生驱动分子事件的认识不断增加，肉瘤为测试新型疗法提供了一个绝佳的平台。在本综述中，我们提供了PKC家族的结构-功能概述、在肉瘤中靶向这些激酶的基本原理以及临床上PKC抑制的进展情况。
