Page 6 - Read Online

Gabriele et al. J Cancer Metastasis Treat 2018;4:17 Journal of Cancer
DOI: 10.20517/2394-4722.2018.06 Metastasis and Treatment

Review Open Access

Prostate cancer cells at a therapeutic gunpoint of
the autophagy process

Fabio Gabriele, Carolina Martinelli, Sergio Comincini
Department of Biology and Biotechnology, University of Pavia, Pavia 27100, Italy.

Correspondence to: Dr. Sergio Comincini, Department of Biology and Biotechnology, University of Pavia, Pavia 27100, Italy.
E-mail: sergio.comincini@unipv.it
How to cite this article: Gabriele F, Martinelli C, Comincini S. Prostate cancer cells at a therapeutic gunpoint of the autophagy
process. J Cancer Metastasis Treat 2018;4:17. http://dx.doi.org/10.20517/2394-4722.2018.06
Received: 24 Jan 2018 First Decision: 26 Feb 2018 Revised: 6 Mar 2018 Accepted: 26 Mar 2018 Published: 19 Apr 2018

Science Editors: Chun Hei Antonio Cheung, Lucio Miele Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang

Abstract
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.

Keywords: Prostate cancer, autophagy, androgen deprivation therapy, mTOR, autophagosome, LC3-II, Beclin-1

PROSTATE CANCER INCIDENCE AND GENETICS
Prostate cancer is a tumor that develops in the prostate, a gland in the male reproductive system. Most
prostate cancers are slow growing but there are cases of aggressive forms. Tumor cells may metastasize
from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may
cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction. In particular,

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.jcmtjournal.com