Xie Tao, Li Si-Jia, Guo Ming-Rui, Wu Yue, Wang Hang-Yu, Zhang Ke, Zhang Xue, Ouyang Liang, Liu Jie
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Cell Prolif. 2015 Apr;48(2):119-39. doi: 10.1111/cpr.12167. Epub 2015 Feb 4.
Autophagy is an evolutionarily conserved lysosomal mechanism implicated in a wide variety of pathological processes, such as cancer. Autophagy can be regulated by a limited number of autophagy-related genes (Atgs) such as oncogenic Bcl-2/Bcl-XL , mTORC1, Akt and PI3KCI, and tumour suppressive proteins PI3KCIII, Beclin-1, Bif-1, p53, DAPKs, PTEN and UVRAG, which play their crucial roles in regulating autophagy-related cancer. As autophagy has a dual role in cancer cells, with tumour-promoting and tumour-suppressing properties, it has become an attractive target for a series of emerging small molecule drugs. In this review, we reveal new discoveries of related small molecules or chemical compounds that can regulate autophagic pathways and lead to pro-death or pro-survival autophagy, in different types of cancer. We discuss the knots between autophagic targets and candidate drugs, in the hope of shedding new light on exploiting new anti-tumour small molecule drugs for future cancer therapy.
自噬是一种进化上保守的溶酶体机制，涉及多种病理过程，如癌症。自噬可由有限数量的自噬相关基因（Atgs）调控，如致癌性Bcl-2/Bcl-XL、mTORC1、Akt和PI3KCI，以及肿瘤抑制蛋白PI3KCIII、Beclin-1、Bif-1、p53、DAPKs、PTEN和UVRAG，它们在调节自噬相关癌症中发挥关键作用。由于自噬在癌细胞中具有促进肿瘤和抑制肿瘤的双重作用，它已成为一系列新兴小分子药物的有吸引力的靶点。在本综述中，我们揭示了相关小分子或化合物的新发现，这些小分子或化合物可调节自噬途径，并在不同类型的癌症中导致促死亡或促生存自噬。我们讨论了自噬靶点与候选药物之间的关系，希望为未来癌症治疗开发新的抗肿瘤小分子药物提供新的思路。
