TY - JOUR
T1 - Autophagic pathways as new targets for cancer drug development
AU - Liu, Bo
AU - Cheng, Yan
AU - Liu, Qian
AU - Bao, Jin Ku
AU - Yang, Jin Ming
PY - 2010/9
Y1 - 2010/9
N2 - Autophagy is an evolutionarily conserved lysosomal self-digestion process involved in degradation of long-lived proteins and damaged organelles. In recent years, increasing evidence indicates that autophagy is associated with a number of pathological processes, including cancer. In this review, we focus on the recent studies of the evolutionarily conserved autophagy-related genes (ATGs) that are implicated in autophagosome formation and the pathways involved. We discuss several key autophagic mediators (eg, Beclin-1, UVRAG, Bcl-2, Class III and I PI3K, mTOR, and p53) that play pivotal roles in autophagic signaling networks in cancer. We discuss the Janus roles of autophagy in cancer and highlighted their relationship to tumor suppression and tumor progression. We also present some examples of targeting ATGs and several protein kinases as anticancer strategy, and discuss some autophagy-modulating agents as antitumor agents. A better understanding of the relationship between autophagy and cancer would ultimately allow us to harness autophagic pathways as new targets for drug discovery in cancer therapeutics.
AB - Autophagy is an evolutionarily conserved lysosomal self-digestion process involved in degradation of long-lived proteins and damaged organelles. In recent years, increasing evidence indicates that autophagy is associated with a number of pathological processes, including cancer. In this review, we focus on the recent studies of the evolutionarily conserved autophagy-related genes (ATGs) that are implicated in autophagosome formation and the pathways involved. We discuss several key autophagic mediators (eg, Beclin-1, UVRAG, Bcl-2, Class III and I PI3K, mTOR, and p53) that play pivotal roles in autophagic signaling networks in cancer. We discuss the Janus roles of autophagy in cancer and highlighted their relationship to tumor suppression and tumor progression. We also present some examples of targeting ATGs and several protein kinases as anticancer strategy, and discuss some autophagy-modulating agents as antitumor agents. A better understanding of the relationship between autophagy and cancer would ultimately allow us to harness autophagic pathways as new targets for drug discovery in cancer therapeutics.
KW - Bcl-2
KW - Class III and I PI3K
KW - autophagy
KW - autophagy-related gene (ATG), Beclin-1
KW - cancer
KW - mTOR
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=77956363593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956363593&partnerID=8YFLogxK
U2 - 10.1038/aps.2010.118
DO - 10.1038/aps.2010.118
M3 - Review article
C2 - 20694022
AN - SCOPUS:77956363593
SN - 1671-4083
VL - 31
SP - 1154
EP - 1164
JO - Acta Pharmacologica Sinica
JF - Acta Pharmacologica Sinica
IS - 9
ER -