The immunotherapy revolution in genitourinary malignancies.
Ontology highlight
ABSTRACT:
SUBMITTER: U Gandhy S
PROVIDER: S-EPMC7466927 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE OF REVIEW:Active investigation suggests immune checkpoint inhibitor therapy and therapeutic cancer vaccines provide clinical benefit for genitourinary malignancies including prostate cancer, renal cell carcinoma, and bladder cancer. Recent developments in the utility of immune checkpoint inhibitor and vaccine therapy for the management of genitourinary malignancies are highlighted in this review. RECENT FINDINGS:Dramatic responses to checkpoint inhibitor therapy have been demonstrated in renal cell carcinoma and bladder cancer with recent Food and Drug Administration approvals in both indications. No benefit to checkpoint inhibitor therapy has yet been shown for the management of prostate cancer. Therapeutic cancer vaccines have also shown benefit in the treatment of genitourinary malignancies, specifically in the treatment of prostate cancer. Despite advances in these therapeutic modalities, benefit is limited to a subset of patients. SUMMARY:Current evidence supports the use of immune checkpoint inhibitor therapy and therapeutic cancer vaccines for the management of genitourinary malignancies. Further development of biomarkers for predicting response and study of combination therapy is required to achieve optimal efficacy with these therapeutic interventions.
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Project description:Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.
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Project description:Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guérin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo. The immune checkpoint inhibitor nivolumab (anti-PD-1) recently received FDA approval for the management of patients with advanced RCC patients previously treated with anti-angiogenic therapy, based on OS benefit compared to everolimus. Recently, large clinical trials demonstrated meaningful clinical benefit, including durable responses, as well as a good tolerability/safety profile with the use of immune checkpoint inhibitors in advanced RCC and chemotherapy-resistant advanced urothelial carcinoma (UC), while FDA just approved atezolizumab for platinum-treated advanced UC. Numerous interesting trials in different cancers are ongoing. Several combinations of immune checkpoint blockade with chemotherapeutics, vaccines, targeted tyrosine kinase inhibitors & monoclonal antibodies, epigenetic modifiers, anti-angiogenic agents, tumor microenvironment & myeloid cell targeting therapies, metabolic modification strategies, radiation, and others, are being tested in clinical trials. Comprehensive understanding of the factors underlying antitumor immune responses in physiologically relevant animal models and humans will refine further the clinical benefit of immunotherapy. Discovery and validation of appropriate molecular biomarkers via coordinated translational research efforts, rational clinical trial designs with suitable endpoints and well-defined eligibility criteria, prospective registries/databases, careful evaluation of cost-effectiveness and safety/tolerability, adequate funding and open continuous discussions among all stakeholders will support the revolutionary nature of immunotherapy in GU cancers.
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Project description:A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer types. In genitourinary malignancies, immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma; however, these treatments have not yet proven broadly beneficial for patients with metastatic prostate cancer. Numerous prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint inhibition. This perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal, urothelial, and prostate cancers.
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Project description:As we learn more about the molecular biology of genitourinary malignancies, novel therapeutic strategies can be developed. This is especially crucial for prostate, renal, and bladder cancer, where mortality rates remain high especially in advanced disease states. The androgen signaling axis and the androgen receptor (AR) are areas that are actively being explored for their role in these diseases. Although long been associated with prostate cancer development and progression, the role of AR in renal cell carcinoma (RCC) and bladder cancer is becoming recognized as well. This review will highlight the current research into the role of the androgen signaling axis in genitourinary malignancies and how this pathway is being used to expand our therapeutic armamentarium.
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