{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:27:05Z","timestamp":1786512425044,"version":"build-2736575974"},"reference-count":142,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia in Katowice","award":["BNW-1-172\/N\/4\/O"],"award-info":[{"award-number":["BNW-1-172\/N\/4\/O"]}]},{"award":["BNW-1-172\/N\/4\/O"],"award-info":[{"award-number":["BNW-1-172\/N\/4\/O"]}],"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Autophagy is a process that diversely impacts the stages of both tumor initiation and progression. Elucidating the molecular mechanisms underlying autophagy and its role in tumorigenesis is a key component of anticancer strategies in both prostate cancer and other malignancies. Because advanced prostate cancer frequently exploits enhanced autophagy as a defense mechanism against therapy-induced stress (e.g., from abiraterone), the pharmacological modulation of miRNA levels presents a tremendous opportunity to block the tumor\u2019s escape route and overcome drug resistance. Methods: A comprehensive literature review was conducted to evaluate the molecular pathways determining cancer cell survival and death. The analysis focused on the dual nature of autophagy (functioning as a \u2018double-edged sword\u2019) within the tumor microenvironment, microRNA (miRNA) regulatory networks, and the efficacy of synergistic therapeutic strategies in overcoming treatment resistance. Results: The primary focus of this paper is the dual and complex role of autophagy, which serves, on the one hand, as a cellular protective shield against metabolic stress\u2014thereby facilitating metastasis\u2014and, on the other hand, as a potential pathway leading to autophagic cell death. The progression of this crucial process is regulated by intricate interactions (crosstalk) with apoptotic pathways, mediated by Bcl-2 family proteins, key kinases (such as mTOR, JNK, and DAPK), and transcription factors, such as p53. Furthermore, the autophagic machinery is precisely regulated by specific miRNA molecules (e.g., miR-21, miR-141, and miR-375). These not only act as crucial intracellular modulators of autophagy but also serve as promising circulating biomarkers, enabling the monitoring of this process\u2019s activity throughout disease progression. Conclusions: Autophagy, and in particular its modulation via miRNA signaling networks, represents a major and highly promising translational target. By directly impairing this autophagic survival mechanism, \u2018double-hit\u2019 combination therapies\u2014integrating autophagy inhibitors (such as hydroxychloroquine or VPS34 inhibitors) with standard antiandrogen or cytotoxic agents\u2014demonstrate promising preclinical potential in overcoming treatment resistance and favorably modulating the immune microenvironment in advanced prostate cancer.<\/jats:p>","DOI":"10.3390\/medsci14040471","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:23:50Z","timestamp":1786357430000},"page":"471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Autophagy in Cancer Evolution and Prognosis, Highlighting Its Role in PCa and Its Interaction with Apoptosis and Epigenetic Regulation by miRNAs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7867-7732","authenticated-orcid":false,"given":"Magdalena","family":"Kurkiewicz","sequence":"first","affiliation":[{"name":"Department of Toxicology, Toxicological Analysis and Bioanalysis, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0779-6019","authenticated-orcid":false,"given":"Aleksandra","family":"Mo\u017adzierz","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Toxicological Analysis and Bioanalysis, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland"},{"name":"Faculty of Medicine, Branch in Bielsko-Bia\u0142a, Medical University of Silesia in Katowice, 43-382 Bielsko-Bia\u0142a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-5765","authenticated-orcid":false,"given":"Anna","family":"Rzepecka-Stojko","sequence":"additional","affiliation":[{"name":"Department of Drug and Cosmetics Technology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-4959","authenticated-orcid":false,"given":"Jerzy","family":"Stojko","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Toxicological Analysis and Bioanalysis, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland"},{"name":"Faculty of Medicine, Branch in Bielsko-Bia\u0142a, Medical University of Silesia in Katowice, 43-382 Bielsko-Bia\u0142a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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