In the normal prostate, controlling cell death is essential to maintain tissue homeostasis and loss of this cell death control may lead to development of cancer. Androgen receptor (AR) signaling plays pivotal roles in the prostate development and homeostasis as well as in the progression of prostate cancer. Androgen deprivation therapy (ADT), with anti-androgens, is still the main treatment for this cancer, together with docetaxil treatment. However, ADT eventually fails due to a variation of cell death processes, in particular apoptosis and autophagy, and 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 treatment resistance. Autophagy is actually often impaired in prostate cancer, due to either activation of the Akt/mTOR pathway, which normally inhibits autophagy, or through allelic loss of the essential autophagy gene Beclin-1. In particular, elucidating the interplay between autophagy and tumor cell metabolism will provide unique opportunities to identify new therapeutic targets and develop synthetically lethal treatment strategies that preferentially target cancer cells, while sparing normal tissues.

Prostate cancer cells at a therapeutic gunpoint of the autophagy process

Sergio Comincini
Supervision
2018-01-01

Abstract

In the normal prostate, controlling cell death is essential to maintain tissue homeostasis and loss of this cell death control may lead to development of cancer. Androgen receptor (AR) signaling plays pivotal roles in the prostate development and homeostasis as well as in the progression of prostate cancer. Androgen deprivation therapy (ADT), with anti-androgens, is still the main treatment for this cancer, together with docetaxil treatment. However, ADT eventually fails due to a variation of cell death processes, in particular apoptosis and autophagy, and 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 treatment resistance. Autophagy is actually often impaired in prostate cancer, due to either activation of the Akt/mTOR pathway, which normally inhibits autophagy, or through allelic loss of the essential autophagy gene Beclin-1. In particular, elucidating the interplay between autophagy and tumor cell metabolism will provide unique opportunities to identify new therapeutic targets and develop synthetically lethal treatment strategies that preferentially target cancer cells, while sparing normal tissues.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1216429
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