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Review

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

1
Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, Canada
2
London Regional Cancer Program, London Health Sciences Centre, Western University, London, ON N6A 5W9, Canada
3
Department of Oncology, Division of Medical Oncology, Schulich School of Medicine & Dentistry, London Health Sciences Centre, Western University, London, ON N6A 5W9, Canada
4
Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
5
Division of Experimental Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5W9, Canada
6
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2022, 29(8), 5426-5441; https://doi.org/10.3390/curroncol29080429
Received: 18 July 2022 / Accepted: 29 July 2022 / Published: 30 July 2022
(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)
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. View Full-Text
Keywords: metastatic renal cell carcinoma; immunotherapy; targeted therapy; new targets; HIF2; microbiome; CAR-T; metabolomics metastatic renal cell carcinoma; immunotherapy; targeted therapy; new targets; HIF2; microbiome; CAR-T; metabolomics
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MDPI and ACS Style

Cardenas, L.M.; Deluce, J.E.; Khan, S.; Gulam, O.; Maleki Vareki, S.; Fernandes, R.; Lalani, A.-K.A. Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma. Curr. Oncol. 2022, 29, 5426-5441. https://doi.org/10.3390/curroncol29080429

AMA Style

Cardenas LM, Deluce JE, Khan S, Gulam O, Maleki Vareki S, Fernandes R, Lalani A-KA. Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma. Current Oncology. 2022; 29(8):5426-5441. https://doi.org/10.3390/curroncol29080429

Chicago/Turabian Style

Cardenas, Luisa M., Jasna E. Deluce, Shahrukh Khan, Omar Gulam, Saman Maleki Vareki, Ricardo Fernandes, and Aly-Khan A. Lalani. 2022. "Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma" Current Oncology 29, no. 8: 5426-5441. https://doi.org/10.3390/curroncol29080429

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