Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors

Sunil Samnani; Faraz Sachedina; Mehul Gupta; Edward Guo; Vishal Navani

doi:10.20517/cdr.2023.02

Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors

Cancer Drug Resist. 2023 Jun 27;6(2):416-429. doi: 10.20517/cdr.2023.02. eCollection 2023.

Authors

Sunil Samnani¹, Faraz Sachedina¹, Mehul Gupta², Edward Guo², Vishal Navani³

Affiliations

¹ Department of Internal Medicine, The University of Calgary, Calgary T2N 1N4, Canada.
² Cumming School of Medicine, University of Calgary, Calgary T2N 4N1, Canada.
³ Department of Medical Oncology, Tom Baker Cancer Centre, Calgary T2N 4N2, Canada.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. The prognosis for patients with ccRCC has improved over recent years with the use of combination therapies with an anti-programmed death-1 (PD-1) backbone. This has enhanced the quality of life and life expectancy of patients with this disease. Unfortunately, not all patients benefit; eventually, most patients will develop resistance to therapy and progress. Recent molecular, biochemical, and immunological research has extensively researched anti-angiogenic and immune-based treatment resistance mechanisms. This analysis offers an overview of the principles underpinning the resistance pathways related to immune checkpoint inhibitors (ICIs). Additionally, novel approaches to overcome resistance that may be considered for the trial context are discussed.

Keywords: Renal cell carcinoma; immunotherapy; intrinsic factors; treatment resistance; tumor microenvironment.

Publication types

Review