The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers

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, prost...

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Main Authors: Ryan Michael Antar, Christopher Fawaz, Diego Gonzalez, Vincent Eric Xu, Arthur Pierre Drouaud, Jason Krastein, Faozia Pio, Andeulazia Murdock, Kirolos Youssef, Stanislav Sobol, Michael J. Whalen
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Current Oncology
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Online Access:https://www.mdpi.com/1718-7729/31/11/511
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author Ryan Michael Antar
Christopher Fawaz
Diego Gonzalez
Vincent Eric Xu
Arthur Pierre Drouaud
Jason Krastein
Faozia Pio
Andeulazia Murdock
Kirolos Youssef
Stanislav Sobol
Michael J. Whalen
author_facet Ryan Michael Antar
Christopher Fawaz
Diego Gonzalez
Vincent Eric Xu
Arthur Pierre Drouaud
Jason Krastein
Faozia Pio
Andeulazia Murdock
Kirolos Youssef
Stanislav Sobol
Michael J. Whalen
author_sort Ryan Michael Antar
collection DOAJ
description 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.
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spelling doaj-art-1ff71cfece1d48eb8eb214195d96b32b2024-11-26T17:58:57ZengMDPI AGCurrent Oncology1198-00521718-77292024-11-0131116909693710.3390/curroncol31110511The Evolving Molecular Landscape and Actionable Alterations in Urologic CancersRyan Michael Antar0Christopher Fawaz1Diego Gonzalez2Vincent Eric Xu3Arthur Pierre Drouaud4Jason Krastein5Faozia Pio6Andeulazia Murdock7Kirolos Youssef8Stanislav Sobol9Michael J. Whalen10Department of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USADepartment of Urology, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USAThe 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.https://www.mdpi.com/1718-7729/31/11/511urologyurologic cancersgenitourinaryprostatebladderrenal cell carcinoma
spellingShingle Ryan Michael Antar
Christopher Fawaz
Diego Gonzalez
Vincent Eric Xu
Arthur Pierre Drouaud
Jason Krastein
Faozia Pio
Andeulazia Murdock
Kirolos Youssef
Stanislav Sobol
Michael J. Whalen
The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
Current Oncology
urology
urologic cancers
genitourinary
prostate
bladder
renal cell carcinoma
title The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
title_full The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
title_fullStr The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
title_full_unstemmed The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
title_short The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers
title_sort evolving molecular landscape and actionable alterations in urologic cancers
topic urology
urologic cancers
genitourinary
prostate
bladder
renal cell carcinoma
url https://www.mdpi.com/1718-7729/31/11/511
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