The discovery in the 1980s that protein kinase C (PKC) is a receptor for the tumor-promoting phorbol esters fueled the dogma that PKC is an oncoprotein. Yet 30+ years of clinical trials for cancer using PKC inhibitors not only failed, but in some instances worsened patient outcome. The recent analysis of cancer-associated mutations, from diverse cancers and throughout the PKC family, revealed that PKC isozymes are generally inactivated in cancer, supporting a tumor suppressive function. In keeping with a bona fide tumor suppressive role, germline causal loss-of-function (LOF) mutations in one isozyme have recently been identified in lymphoproliferative disorders. Thus, strategies in cancer treatment should focus on restoring rather than inhibiting PKC.

在1980年代，发现蛋白激酶C（PKC）是促肿瘤的佛波醇酯的受体，这促使教条认为PKC是一种癌蛋白。然而，使用PKC抑制剂进行癌症的30多年临床试验不仅失败了，而且在某些情况下恶化了患者的预后。最近对来自各种癌症以及整个PKC家族的癌症相关突变的分析表明，PKC同工酶通常在癌症中失活，从而具有抑制肿瘤的功能。为了保持真正的肿瘤抑制作用，最近在淋巴增生性疾病中发现了一种同工酶的种系因果功能丧失（LOF）突变。因此，癌症治疗中的策略应侧重于恢复而不是抑制PKC。