Sun Ting, Liu Hongchun, Ming Liang
Cell Physiol Biochem. 2017;44(2):716-727. doi: 10.1159/000485285. Epub 2017 Nov 23.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and prognosis remains unsatisfactory since the disease is often diagnosed at the advanced stages. Currently, the multikinase inhibitor sorafenib is the only drug approved for the treatment of advanced HCC. However, primary or acquired resistance to sorafenib develops, generating a roadblock in HCC therapy. Autophagy is an intracellular lysosomal pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. Current understanding of the role of autophagy in the progression of cancer and the response to cancer therapy remains controversial. Sorafenib is able to induce autophagy in HCC, but the effect of autophagy is indistinct. Some studies established that sorafenib-induced autophagy serves as a pro-survival response. However, other studies found that sorafenib-induced autophagy improves the lethality of sorafenib against HCC cells. The mechanisms underlying autophagy and sorafenib resistance remain elusive. The purpose of this review is to summarize the progress of research focused on autophagy and sorafenib resistance and to update current knowledge of how cellular autophagy impacts sorafenib sensitivity in HCC treatment.
肝细胞癌（HCC）是全球癌症相关死亡的第二大主要原因，由于该病往往在晚期才被诊断出来，其预后仍然不尽人意。目前，多激酶抑制剂索拉非尼是唯一被批准用于治疗晚期HCC的药物。然而，对索拉非尼会产生原发性或获得性耐药，这在HCC治疗中形成了障碍。自噬是一种细胞内溶酶体途径，参与蛋白质和细胞器的降解，与人类疾病和生理学有着惊人数量的联系。目前对于自噬在癌症进展和癌症治疗反应中的作用的理解仍存在争议。索拉非尼能够在HCC中诱导自噬，但其自噬效应并不明确。一些研究表明，索拉非尼诱导的自噬起到促生存反应的作用。然而，其他研究发现，索拉非尼诱导的自噬提高了索拉非尼对HCC细胞的杀伤力。自噬和索拉非尼耐药的潜在机制仍然不清楚。这篇综述的目的是总结关于自噬和索拉非尼耐药的研究进展，并更新目前关于细胞自噬如何影响HCC治疗中索拉非尼敏感性的知识。
