Open AccessKey autophagic targets and relevant small‐molecule compounds in cancer therapy
Author(s) -
Tong X.P,
Chen Y.,
Zhang S.Y.,
Xie T.,
Tian M.,
Guo M.R.,
Kasimu R.,
Ouyang L.,
Wang J.H.
Publication year - 2015
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12154
Subject(s) - autophagy , pi3k/akt/mtor pathway , mtorc1 , protein kinase b , cancer , biology , cancer research , cancer cell , programmed cell death , microbiology and biotechnology , signal transduction , apoptosis , biochemistry , genetics
Autophagy is a highly conserved lysosomal degradation process which can recycle unnecessary or dysfunctional cell organelles and proteins, thereby playing a crucial regulatory role in cell survival and maintenance. It has been widely accepted that autophagy regulates various pathological processes, among which cancer attracts much attention. Autophagy may either promote cancer cell survival by providing energy during unfavourable metabolic circumstance or can induce individual cancer cell death by preventing necrosis and increasing genetic instability. Thus, dual roles of autophagy may determine the destiny of cancer cells and make it an attractive target for small‐molecule drug discovery. Collectively, key autophagy‐related elements as potential targets, oncogenes mTORC1 , class I PI3K and AKT , as well as tumour suppressor class III PI3K , Beclin‐1 and p53 , have been discussed. In addition, some small molecule drugs, such as rapamycin and its derivatives, rottlerin, PP242 and AZD8055 (targeting PI3K/AKT/ mTORC 1), spautin‐1, and tamoxifen, as well as oridonin and metformin (targeting p53), can modulate autophagic pathways in different types of cancer. All these data will shed new light on targeting the autophagic process for cancer therapy, using small‐molecule compounds, to fight cancer in the near future.