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Prostate cancer cells at a therapeutic gunpoint of the autophagy process
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作者 Fabio Gabriele carolina martinelli Sergio Comincini 《Journal of Cancer Metastasis and Treatment》 CAS 2018年第1期210-226,共17页
In a normal prostate,the process of controling cell death is essential to maintain tissue homeostasis and its inhibition may lead to the development of cancer.Androgen receptor signaling plays pivotal roles in the pro... In a normal prostate,the process of controling cell death is essential to maintain tissue homeostasis and its inhibition may lead to the development of cancer.Androgen receptor signaling plays pivotal roles in the prostate development and homeostasis as well as in the progression of prostate cancer.The main treatment for prostate cancer is a combination of androgen deprivation therapy(ADT)using anti-androgens and docetaxil administration.However,ADT eventually fails due to a pathological unbalance of cell death processes,in particular apoptosis and autophagy.As a result prostate tumors may re-grow and progress into the castration resistant stage.The role of autophagy in tumorigenesis is complex and it could be a double-edged sword process,as autophagy defects promote cancer progression in association with various dangerous cellular processes,while functional autophagy enables cancer cell survival under stress and likely contributes to the resistance of treatment.Autophagy is often impaired in prostate cancer,due to either activation of the Akt/mTOR pathway,which normally inhibits autophagy,or through allelic loss of Beclin-1(BECN1),an essential autophagy gene.In particular,elucidating the interplay between autophagy and tumor cell metabolism will provide unique opportunities to identify new therapeutic targets and to develop synthetically lethal treatment strategies that preferentially target cancer cells,while sparing normal tissues. 展开更多
关键词 Prostate cancer AUTOPHAGY androgen deprivation therapy mTOR AUTOPHAGOSOME LC3-Ⅱ BECLIN-1
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