Alastair Davies1, Vincenza Conteduca2, Amina Zoubeidi3, Himisha Beltran4. 1. Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. 2. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 3. Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address: azoubeidi@prostatecentre.com. 4. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: himisha_beltran@dfci.harvard.edu.
Abstract
CONTEXT: Recent studies focused on the molecular characterization of metastatic prostate cancer have identified genomic subsets and emerging resistance patterns. Detection of these alterations in patients has potential implications for therapy selection and prognostication. OBJECTIVE: The primary objective is to review the current landscape of clinical and molecular biomarkers in advanced prostate cancer and understand how they may reflect underlying tumor biology. We also discuss how these features may potentially impact earlier stages of the disease. EVIDENCE ACQUISITION: A literature search was performed of recent clinical biomarker/genomic studies focused on advanced metastatic prostate cancer as well as relevant preclinical studies investigating how these alterations influence therapy response or resistance. EVIDENCE SYNTHESIS: Metastatic castration-resistant prostate cancer is commonly driven by androgen receptor signaling even after progression on potent hormonal agents, but other alterations may also be present or emerge during therapy resistance such as DNA repair gene aberrations or combined loss of tumor suppressor genes. Biological implications of these changes are context dependent, which may affect their detection and interpretation. CONCLUSIONS: Molecular changes occur during prostate cancer progression and treatment resistance. Detection of genomic alterations has potential to influence therapy choice. Additional studies are warranted to elucidate the evolution of these changes and their impact in earlier stages of the disease. PATIENT SUMMARY: We review the biology of advanced prostate cancer, and highlight opportunities and challenges for using biological or molecular assays to help guide individualized treatment decisions for patients.
CONTEXT: Recent studies focused on the molecular characterization of metastatic prostate cancer have identified genomic subsets and emerging resistance patterns. Detection of these alterations in patients has potential implications for therapy selection and prognostication. OBJECTIVE: The primary objective is to review the current landscape of clinical and molecular biomarkers in advanced prostate cancer and understand how they may reflect underlying tumor biology. We also discuss how these features may potentially impact earlier stages of the disease. EVIDENCE ACQUISITION: A literature search was performed of recent clinical biomarker/genomic studies focused on advanced metastatic prostate cancer as well as relevant preclinical studies investigating how these alterations influence therapy response or resistance. EVIDENCE SYNTHESIS: Metastatic castration-resistant prostate cancer is commonly driven by androgen receptor signaling even after progression on potent hormonal agents, but other alterations may also be present or emerge during therapy resistance such as DNA repair gene aberrations or combined loss of tumor suppressor genes. Biological implications of these changes are context dependent, which may affect their detection and interpretation. CONCLUSIONS: Molecular changes occur during prostate cancer progression and treatment resistance. Detection of genomic alterations has potential to influence therapy choice. Additional studies are warranted to elucidate the evolution of these changes and their impact in earlier stages of the disease. PATIENT SUMMARY: We review the biology of advanced prostate cancer, and highlight opportunities and challenges for using biological or molecular assays to help guide individualized treatment decisions for patients.
Authors: Vincenza Conteduca; Sheng-Yu Ku; Loredana Puca; Megan Slade; Luisa Fernandez; Judy Hess; Rohan Bareja; Panagiotis J Vlachostergios; Michael Sigouros; Juan Miguel Mosquera; Andrea Sboner; David M Nanus; Olivier Elemento; Ryan Dittamore; Scott T Tagawa; Himisha Beltran Journal: Mol Cancer Ther Date: 2020-03-03 Impact factor: 6.261
Authors: Vicenç Ruiz de Porras; Juan Carlos Pardo; Lucia Notario; Olatz Etxaniz; Albert Font Journal: Int J Mol Sci Date: 2021-04-29 Impact factor: 5.923