Special Issue "Beyond Immunotherapy in the Management of Genito-Urinary Malignancies"

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Genitourinary Oncology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 6759

Special Issue Editors

Dr. Ricardo Fernandes
E-Mail Website
Guest Editor
Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5W9, Canada
Interests: genito-urinary malignancies; early phase drug trials; immunotherapy; predictive biomarkers and microbiome studies
Dr. Aly-Khan Lalani
E-Mail Website
Guest Editor
Juravinski Cancer Centre, Department of Oncology, McMaster University, Hamilton, Ontario L8S 4L8, Canada
Interests: genito-urinary malignancies; novel trial design; immunotherapy; biomarkers; microbiome studies

Special Issue Information

Dear Colleagues,

Immunotherapy with immune checkpoint inhibitors (ICIs) has changed oncology practice in the last decade. The members of this class of agents include: ipilimumab, a cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor; nivolumab and pembrolizumab, antiprogrammed cell death 1 (PD-1) agents; atezolizumab, durvalumab, and avelumab, which are antiprogrammed cell death-ligand 1 (PD-L1) agents. ICIs have become the standard treatment in genito-urinary malignancies, including first-line and second-line treatments for renal cell carcinoma and urothelial carcinoma.

Despite the clinical efficacy of the checkpoint blockade, most cancer patients still do not derive durable benefits from these therapies. Moreover, ICIs can induce various immune-related adverse events (irAEs), limiting their use in many patients. ICIs may affect peripheral tolerance to autoantigens, resulting in autoantibody formation, which could be associated with irAEs in various organs. Therefore, there is a need for additional therapeutic approaches. Several clinical trials are ongoing with different therapies, including chemotherapy, antibody–drug conjugates, agents targeting additional immune checkpoint pathways, vaccines, cytokines, adoptive cell therapies, as well as targeted and antiangiogenic agents. The biology of each disease and optimal sequencing of active therapies are key points that are being evaluated in prospective clinical trials. Current challenges include molecular heterogeneity, clonal evolution, genomic instability, identifying and utilizing biomarkers that predict survival and/or treatment response, and identifying optimal tools to help guide precision medicine.

This Special Issue aims to review biological underpinnings, clinical strategies and potential future directions of promising therapeutic targets in uro-oncology and how this knowledge may inform the future landscape of these diseases.

Dr. Ricardo Fernandes
Dr. Aly-Khan Lalani
Guest Editors

Manuscript Submission Information

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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. Current Oncology is an international peer-reviewed open access monthly 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 1800 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

  • immunotherapy
  • immune checkpoint inhibitors
  • genito-urinary malignancies
  • precision medicine

Published Papers (5 papers)

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Review

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Review
Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma
Curr. Oncol. 2022, 29(8), 5426-5441; https://doi.org/10.3390/curroncol29080429 - 30 Jul 2022
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Abstract
While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell [...] Read more.
While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell death 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have become globally accepted options in the upfront metastatic setting, with different ICI-based combination strategies improving overall survival compared to single-agent Sunitinib. Although some patients benefit from long-term responses, most eventually develop disease progression. Ongoing efforts to better understand the biology of RCC and the different mechanisms of acquired resistance have led to the identification of promising therapeutic targets. Belzutifan, a novel agent targeting the angiogenic pathway involving hypoxia-inducible factors (HIFs), has already been approved for the treatment of early-stage tumors associated with VHL disease and represents a very promising therapy in advanced RCC. Other putative targets include epigenetic regulation enzymes, as well as several metabolites such as adenosine, glutaminase and tryptophan, which are critical players in cancer cell metabolism and in the tumor microenvironment. Different methods of immune regulation are also being investigated, including CAR-T cell therapy and modulation of the gut microbiome, in addition to novel agents targeting the interleukin-2 (IL-2) pathway. This review aims to highlight the emergent novel therapies for RCC and their respective completed and ongoing clinical trials. Full article
(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)
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Review
Emerging Biomarker-Guided Therapies in Prostate Cancer
Curr. Oncol. 2022, 29(7), 5054-5076; https://doi.org/10.3390/curroncol29070400 - 18 Jul 2022
Cited by 1 | Viewed by 1511
Abstract
Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and [...] Read more.
Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy. Full article
(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)
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Case Report
Sintilimab-Induced Diabetic Ketoacidosis in a Patient with Radiation and Multichemorefractory Penile Cancer: A Case Report and Literature Review
Curr. Oncol. 2022, 29(11), 7987-7993; https://doi.org/10.3390/curroncol29110632 - 25 Oct 2022
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Abstract
Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). [...] Read more.
Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection, and excision of the abdominal wall mass. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin then being carried out, the carcinoma still progressed. The patient then obtained progression-free survival with continuous sintilimab, although he experienced the new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He had negative type 1 diabetes-associated autoantibodies and the susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory PSCC who has obtained the remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab and anlotinib treatment. Full article
(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)
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Case Report
Rare and Insidious Toxicities from New Combination Therapies in Metastatic Renal Cell Cancer: Lessons Learned from Real-Practice
Curr. Oncol. 2022, 29(10), 6776-6786; https://doi.org/10.3390/curroncol29100533 - 22 Sep 2022
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Abstract
The advent of immune checkpoint inhibitors in combination with multitarget tyrosine kinase inhibitors has become a standard first-line treatment for metastatic renal cell cancer. Along with survival improvement, new toxicities have emerged. Such adverse events are still complex to be managed and some [...] Read more.
The advent of immune checkpoint inhibitors in combination with multitarget tyrosine kinase inhibitors has become a standard first-line treatment for metastatic renal cell cancer. Along with survival improvement, new toxicities have emerged. Such adverse events are still complex to be managed and some of them are rare and could be insidious or even fatal. Medical oncologists dispose of guidelines about the management of toxicities from immune checkpoint inhibitors but not for combinations. Therefore, it is still difficult to properly attribute and manage additive or overlapping adverse events. We report two clinical cases regarding rare treatment-related endocrine toxicities—hypophysitis and thyroiditis—with particular focus on their management. To this purpose, immune checkpoint-related toxicities guidelines represent the starting point. However, their implementation with additional measures is needed, considering the increasing complexity of current clinical scenarios. The goal is to correctly recognize adverse events and address side effects, so as not to discontinue effective treatments. We, therefore, aim at discussing the points of proper management of toxicities and individuating potential areas of improvement. Full article
(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)
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Case Report
Response to Combination of Pembrolizumab and Axitinib in Hereditary Leyomiomatosis and Renal Cell Cancer (HLRCC)
Curr. Oncol. 2021, 28(4), 2346-2350; https://doi.org/10.3390/curroncol28040216 - 25 Jun 2021
Cited by 1 | Viewed by 1182
Abstract
In current clinical guidelines, such as those provided by the National Comprehensive Cancer Network (NCCN), evidence for treatment is based on a small clinical trial that included patients with HLRCC. They support the use of the combination of erlotinib and bevacizumab as the [...] Read more.
In current clinical guidelines, such as those provided by the National Comprehensive Cancer Network (NCCN), evidence for treatment is based on a small clinical trial that included patients with HLRCC. They support the use of the combination of erlotinib and bevacizumab as the first therapeutic option in this rare condition. In the present study, we report a rare case of this condition in an 18-year-old male with a family history of kidney cancer whom we successfully treated with surgery and a novel drug treatment modality based on the combination of an immune check-point inhibitor (ICPI) and a tyrosine-kinase inhibitor (TKI) with excellent and promising results. Full article
(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)
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