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Cancers
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Novel Therapeutics for Genitourinary Tumors
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Novel Therapeutics for Genitourinary Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 18267

Special Issue Editor

Dr. Arnab Basu

E-Mail Website
Guest Editor
Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Interests: kidney cancer; bladder cancer; prostate cancer; immunotherapy; MDSC; novel therapeutics

Special Issue Information

Dear Colleagues, 

This is a very exciting time in genitourinary oncology. Over the past few years, chemotherapeutic regimens have been bolstered and, on some occasions, supplanted by the development of novel therapeutic agents that now help our patients live longer and more productive lives. Given the rapid progress in this field, Cancers is publishing a Special Issue focused on the new therapeutic agents approved over the last 5 years (2017–2021) and those that are poised to change the treatment paradigm in the near future. We would be delighted if you (in association with your colleagues), would like to contribute an article to our Special Issue titled ‘Novel Therapeutics for Genitourinary Tumors: 2022 and beyond’. We are looking for articles that summarize new changes in treatments for localized and advanced disease, as well as novel agents such as ADCs, Cellular Therapies, and newly discovered targets. I look forward to hearing from you soon.

Dr. Arnab Basu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • PARP inhibitors
  • CAR-T cells
  • PD-1 inhibitors
  • bladder cancer
  • prostate cancer
  • kidney cancer
  • PSMA-Bite
  • theranostics

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

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Research

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18 pages, 4776 KiB  
Article
Differential Gene Expression Profiles between N-Terminal Domain and Ligand-Binding Domain Inhibitors of Androgen Receptor Reveal Ralaniten Induction of Metallothionein by a Mechanism Dependent on MTF1
by Jon K. Obst, Nasrin R. Mawji, Simon J. L. Teskey, Jun Wang and Marianne D. Sadar
Cancers 2022, 14(2), 386; https://doi.org/10.3390/cancers14020386 - 13 Jan 2022
Cited by 4 | Viewed by 2277
Abstract
Hormonal therapies for prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD). Clinical development for inhibitors that bind to the N-terminal domain (NTD) of AR has yielded ralaniten and its analogues. Ralaniten acetate is well tolerated in patients at 3600 mgs/day. Clinical [...] Read more.
Hormonal therapies for prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD). Clinical development for inhibitors that bind to the N-terminal domain (NTD) of AR has yielded ralaniten and its analogues. Ralaniten acetate is well tolerated in patients at 3600 mgs/day. Clinical trials are ongoing with a second-generation analogue of ralaniten. Binding sites on different AR domains could result in differential effects on AR-regulated gene expression. Here, we provide the first comparison between AR-NTD inhibitors and AR-LBD inhibitors on androgen-regulated gene expression in prostate cancer cells using cDNA arrays, GSEA, and RT-PCR. LBD inhibitors and NTD inhibitors largely overlapped in the profile of androgen-induced genes that they each inhibited. However, androgen also represses gene expression by various mechanisms, many of which involve protein–protein interactions. De-repression of the transcriptome of androgen-repressed genes showed profound variance between these two classes of inhibitors. In addition, these studies revealed a unique and strong induction of expression of the metallothionein family of genes by ralaniten by a mechanism independent of AR and dependent on MTF1, thereby suggesting this may be an off-target. Due to the relatively high doses that may be encountered clinically with AR-NTD inhibitors, identification of off-targets may provide insight into potential adverse events, contraindications, or poor efficacy. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
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Review

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19 pages, 1017 KiB  
Review
Precision Medicine to Treat Urothelial Carcinoma—The Way Forward
by Carvy Floyd Luceno, Won Jin Jeon, Ravand Samaeekia, John Shin and Guru P. Sonpavde
Cancers 2023, 15(11), 3024; https://doi.org/10.3390/cancers15113024 - 1 Jun 2023
Cited by 2 | Viewed by 2329
Abstract
The treatment of urothelial carcinoma (UC) is challenging given its molecular heterogeneity and variable response to current therapies. To address this, many tools, including tumor biomarker assessment and liquid biopsies, have been developed to predict prognosis and treatment response. Approved therapeutic modalities for [...] Read more.
The treatment of urothelial carcinoma (UC) is challenging given its molecular heterogeneity and variable response to current therapies. To address this, many tools, including tumor biomarker assessment and liquid biopsies, have been developed to predict prognosis and treatment response. Approved therapeutic modalities for UC currently include chemotherapy, immune checkpoint inhibitors, receptor tyrosine kinase inhibitors, and antibody drug conjugates. Ongoing investigations to improve the treatment of UC include the search for actionable alterations and the testing of novel therapies. An important objective in recent studies has been to increase efficacy while decreasing toxicity by taking into account unique patient and tumor-related factors—an endeavor called precision medicine. The aim of this review is to highlight advancements in the treatment of UC, describe ongoing clinical trials, and identify areas for future study in the context of precision medicine. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
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13 pages, 521 KiB  
Review
Metastatic Prostate Cancer—A Review of Current Treatment Options and Promising New Approaches
by Philip Posdzich, Christopher Darr, Thomas Hilser, Milan Wahl, Ken Herrmann, Boris Hadaschik and Viktor Grünwald
Cancers 2023, 15(2), 461; https://doi.org/10.3390/cancers15020461 - 11 Jan 2023
Cited by 54 | Viewed by 8190
Abstract
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate [...] Read more.
Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate cancer, combination therapies of two or three agents of ADT, androgen receptor signaling inhibitors (ARSI) and chemotherapy have been established and led to a significant benefit in overall survival. Additionally, in patients with metastatic castration-resistant prostate cancer, there are many new therapeutic approaches. Chemotherapy alone has been the standard of care in this situation. In the last years, some new therapeutic options have been developed, which led to an improved survival after progression under chemotherapy. These therapies include ARSI, PARP inhibitors and Lu-PSMA radioligand therapy. The use of a bispecific T-cell engager (BiTE) in this setting is a new promising therapeutic approach, which has not been established as standard of care yet. The role of immunotherapy in prostate cancer is still under investigation. Overall, many new treatment options make prostate cancer therapy a challenging and promising field. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
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16 pages, 332 KiB  
Review
Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade
by Mathieu Larroquette, Félix Lefort, Luc Heraudet, Jean-Christophe Bernhard, Alain Ravaud, Charlotte Domblides and Marine Gross-Goupil
Cancers 2022, 14(24), 6230; https://doi.org/10.3390/cancers14246230 - 17 Dec 2022
Cited by 6 | Viewed by 2286
Abstract
Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by VHL gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer [...] Read more.
Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by VHL gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010–2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
14 pages, 295 KiB  
Review
Treatment of Refractory Metastatic Renal Cell Carcinoma
by Joseph A. Vento and Brian I. Rini
Cancers 2022, 14(20), 5005; https://doi.org/10.3390/cancers14205005 - 13 Oct 2022
Cited by 13 | Viewed by 2395
Abstract
First-line treatment for metastatic renal cell carcinoma (mRCC) rapidly shifted in recent years with the advent of combination therapies, including immune checkpoint inhibitor (ICI) doublets and combinations of an ICI with a vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitor (TKI). [...] Read more.
First-line treatment for metastatic renal cell carcinoma (mRCC) rapidly shifted in recent years with the advent of combination therapies, including immune checkpoint inhibitor (ICI) doublets and combinations of an ICI with a vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitor (TKI). Despite improvements in overall survival and many durable responses, there exists a significant number of patients who fail to respond to these agents, and many patients eventually progress. Given the rapid changes in the front-line setting, it is essential to understand treatment options in refractory mRCC. Here, we review the evidence behind current options for later-line therapies, often involving additional VEGFR-TKIs alone or in combination with mammalian target of rapamycin (mTOR) targeted agents, as well as situations where consideration of immunotherapy rechallenge may be appropriate. Additionally, we describe ongoing clinical trials examining concurrent ICI and TKI in the refractory setting, as well as those studying novel agents, such as targeted drug–antibody conjugates and hypoxia inducible factor 2α (HIF-2α) inhibitors. Finally, we review considerations for non-clear cell histologies in the refractory setting and mechanisms of resistance in mRCC. Full article
(This article belongs to the Special Issue Novel Therapeutics for Genitourinary Tumors)
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