BACKGROUND: The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy. However, a fraction of men relapse after initial treatment because they develop drug resistance. The failure of anticancer drugs leaves resistant cancer cells to survive and proliferate, negatively affecting patient survival. Thus, drug resistance remains a significant obstacle to the effective treatment of prostate cancer patients. In this scenario, the involvement of extracellular vesicles (EVs) in intrinsic and acquired resistance have been reported in several tumors, and accumulating data suggests that their differential content can be used as diagnostic or prognostic factors. Thus, we propose a systematic study of literature to provide a snapshot of the current scenario regarding EVs as diagnostic and prognostic biomarkers resource in resistant prostate cancer. METHODS: We performed the current systematic review according to PRISMA guidelines and comprehensively explored PubMed, EMBASE and Google Scholar databases to achieve the article search. RESULTS: Thirty-three studies were included and investigated. Among all systematically reviewed EV biomarkers, we found mainly molecules with prognostic significance (61%), molecules with diagnostic relevance (18%), and molecules that serve both purposes (21%). Moreover, among all analyzed molecules isolated from EVs, proteins, mRNAs, and miRNAs emerged to be the most investigated and proposed as potential tools to diagnose or predict resistance/sensitivity to advanced PCa treatments. DISCUSSION: Our analysis provides a snapshot of the current scenario regarding EVs as potential clinical biomarkers in resistant PCa. Nevertheless, despite many efforts, the use of EV biomarkers in PCa is currently at an early stage: none of the selected EV biomarkers goes beyond preclinical studies, and their translatability is yet far from clinical settings.
BACKGROUND: The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy. However, a fraction of men relapse after initial treatment because they develop drug resistance. The failure of anticancer drugs leaves resistant cancer cells to survive and proliferate, negatively affecting patient survival. Thus, drug resistance remains a significant obstacle to the effective treatment of prostate cancer patients. In this scenario, the involvement of extracellular vesicles (EVs) in intrinsic and acquired resistance have been reported in several tumors, and accumulating data suggests that their differential content can be used as diagnostic or prognostic factors. Thus, we propose a systematic study of literature to provide a snapshot of the current scenario regarding EVs as diagnostic and prognostic biomarkers resource in resistant prostate cancer. METHODS: We performed the current systematic review according to PRISMA guidelines and comprehensively explored PubMed, EMBASE and Google Scholar databases to achieve the article search. RESULTS: Thirty-three studies were included and investigated. Among all systematically reviewed EV biomarkers, we found mainly molecules with prognostic significance (61%), molecules with diagnostic relevance (18%), and molecules that serve both purposes (21%). Moreover, among all analyzed molecules isolated from EVs, proteins, mRNAs, and miRNAs emerged to be the most investigated and proposed as potential tools to diagnose or predict resistance/sensitivity to advanced PCa treatments. DISCUSSION: Our analysis provides a snapshot of the current scenario regarding EVs as potential clinical biomarkers in resistant PCa. Nevertheless, despite many efforts, the use of EV biomarkers in PCa is currently at an early stage: none of the selected EV biomarkers goes beyond preclinical studies, and their translatability is yet far from clinical settings.
Authors: Caroline M A Hoeks; Jelle O Barentsz; Thomas Hambrock; Derya Yakar; Diederik M Somford; Stijn W T P J Heijmink; Tom W J Scheenen; Pieter C Vos; Henkjan Huisman; Inge M van Oort; J Alfred Witjes; Arend Heerschap; Jurgen J Fütterer Journal: Radiology Date: 2011-10 Impact factor: 11.105
Authors: Howard I Scher; Karim Fizazi; Fred Saad; Mary-Ellen Taplin; Cora N Sternberg; Kurt Miller; Ronald de Wit; Peter Mulders; Kim N Chi; Neal D Shore; Andrew J Armstrong; Thomas W Flaig; Aude Fléchon; Paul Mainwaring; Mark Fleming; John D Hainsworth; Mohammad Hirmand; Bryan Selby; Lynn Seely; Johann S de Bono Journal: N Engl J Med Date: 2012-08-15 Impact factor: 91.245
Authors: Bijaya Malla; Kathrin Zaugg; Erik Vassella; Daniel M Aebersold; Alan Dal Pra Journal: Int J Radiat Oncol Biol Phys Date: 2017-03-27 Impact factor: 7.038
Authors: Charles J Ryan; Matthew R Smith; Johann S de Bono; Arturo Molina; Christopher J Logothetis; Paul de Souza; Karim Fizazi; Paul Mainwaring; Josep M Piulats; Siobhan Ng; Joan Carles; Peter F A Mulders; Ethan Basch; Eric J Small; Fred Saad; Dirk Schrijvers; Hendrik Van Poppel; Som D Mukherjee; Henrik Suttmann; Winald R Gerritsen; Thomas W Flaig; Daniel J George; Evan Y Yu; Eleni Efstathiou; Allan Pantuck; Eric Winquist; Celestia S Higano; Mary-Ellen Taplin; Youn Park; Thian Kheoh; Thomas Griffin; Howard I Scher; Dana E Rathkopf Journal: N Engl J Med Date: 2012-12-10 Impact factor: 91.245
Authors: Tomasz M Beer; Andrew J Armstrong; Dana E Rathkopf; Yohann Loriot; Cora N Sternberg; Celestia S Higano; Peter Iversen; Suman Bhattacharya; Joan Carles; Simon Chowdhury; Ian D Davis; Johann S de Bono; Christopher P Evans; Karim Fizazi; Anthony M Joshua; Choung-Soo Kim; Go Kimura; Paul Mainwaring; Harry Mansbach; Kurt Miller; Sarah B Noonberg; Frank Perabo; De Phung; Fred Saad; Howard I Scher; Mary-Ellen Taplin; Peter M Venner; Bertrand Tombal Journal: N Engl J Med Date: 2014-06-01 Impact factor: 91.245