Anti-angiogenesis and Immunotherapy: Novel Paradigms to Envision Tailored Approaches in Renal Cell-Carcinoma

Abstract

Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintains and reinforces their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.

Keywords: angiogenesis; immune-checkpoint inhibitor; molecular subtypes; predictive factors; prognostic-biomarkers; renal cell carcinoma; tumor microenvironment.

Figure 1

MSKCC Model (Motzer et al.) and International Metastatic RCC Database Consortium (IMDC) Model (Heng et al.): risk categories and relative median survivals in renal cell carcinoma [13,40,41,42]. The color code represents the presence of a given prognostic factors for each model: PS, Hb, LDH, corrected Ca, time from diagnosis to treatment (red) for MSKCC model; PS, Hb, corrected Ca, time from diagnosis to treatment, NE, PLT (green) for IMDC model.

Figure 2

Systemic treatment of clear-cell renal cell carcinoma according to IMDC prognostic system. * Only EMA approval, ^# Only FDA approval.