The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers

Authors

Ryan Michael Antar, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Christopher Fawaz, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Diego Gonzalez, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Vincent Eric Xu, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Arthur Pierre Drouaud, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Jason Krastein, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Faozia Pio, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Andeulazia Murdock, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Kirolos Youssef, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Stanislav Sobol, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
Michael J. Whalen, Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.

Document Type

Journal Article

Publication Date

11-6-2024

Journal

Current oncology (Toronto, Ont.)

Volume

31

Issue

11

DOI

10.3390/curroncol31110511

Keywords

bladder; genetic mutations; genitourinary; molecular alterations; penile; prostate; renal cell carcinoma; testicular; urologic cancers; urology

Abstract

The genetic landscape of urologic cancers has evolved with the identification of actionable mutations that impact diagnosis, prognosis, and therapeutic strategies. This narrative review consolidates existing literature on genetic mutations across key urologic cancers, including bladder, renal, prostate, upper tract urothelial, testicular, and penile. The review highlights mutations in DNA damage repair genes, such as BRCA1/2 and PTEN, as well as pathway alterations like FGFR and PD-L1 overexpression. These mutations influence tumor behavior and therapeutic outcomes, emphasizing the need for precision oncology approaches. Molecular profiling, through tools like next-generation sequencing, has revolutionized patient care by enabling targeted treatment strategies, especially in cancers with distinct molecular subtypes such as luminal or basal bladder cancer and clear cell renal carcinoma. Emerging therapies, including FGFR inhibitors and immune checkpoint blockade, offer new treatment avenues, although resistance mechanisms remain a challenge. We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes.

APA Citation

Antar, Ryan Michael; Fawaz, Christopher; Gonzalez, Diego; Xu, Vincent Eric; Drouaud, Arthur Pierre; Krastein, Jason; Pio, Faozia; Murdock, Andeulazia; Youssef, Kirolos; Sobol, Stanislav; and Whalen, Michael J., "The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers" (2024). GW Authored Works. Paper 6030.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6030

Department

Urology