Current Management Strategy for Metastatic Renal Cell Carcinoma and Future Directions

Abstract

Most recently, several new drugs including nivolumab, cabozantinib, and a combination of lenvatinib and everolimus have demonstrated acceptable toxicity and significantly improved overall survival, but evidence-based guidelines for sequencing of the approved treatment options and treatment selection based on biomarkers are still missing. Despite the significant progress, many questions still remain unanswered. Several ongoing clinical trials are evaluating sequencing, timing of cytoreductive nephrectomy, combinations of immunotherapies and targeted therapies as well as selection of the best systemic treatment. Personalized treatment based on tumor profiling is one of the brightest spots on the horizon.

Cabozantinib‐induced renal thrombotic microangiopathy

“…In 2012, cabozantinib was approved for treatment of metastatic medullary thyroid cancer . Subsequent clinical trials have been conducted in various malignant neoplasms, in particular gastric, renal cell, pancreatic, and prostate cancer previously treated with other therapy or strategies . The most common adverse events included diarrhoea, nausea, palmar–plantar erythrodysesthesia syndrome, hypertension and proteinuria .…”

Translocating a High-Affinity Designer TIMP-1 to the Cell Membrane for Total Renal Carcinoma Inhibition: Putting the Prion Protein to Good Use

“…26 kDa) was noticeably lower than that of T1 Pr (ca. 28 kDa), owing to the elimination of one of its N-linked glycosylation sites (residue N 30 ) during the process of site-directed mutagenesis (T1 WT sequence EVN 30 QT, T1 TACE mutant sequence EVN 30 QG [residues 30 and 32 are boldface] [boxed in Fig. 1A]) (16).…”

“…In this report, we describe how a soluble designer TIMP-1, named T1 TACE , that has dual potencies for MT1-MMP and TACE can be targeted to the cell membrane for renal carcinoma (CaKi-1) inhibition by fusion with the prion protein (named T1 Pr ␣TACE here). Renal carcinomas are highly metastatic and refractive cancers for which there is no effective chemotherapy or radiation treatment (29,30). Immunohistochemistry and mRNA analysis on clinical samples indicate that MT1-MMP and TACE are often overexpressed in renal carcinoma tissues, and inactivation of the proteinases may provide an effective means of blocking interleukin-1␤-and Notch-mediated cancer cell invasion (31)(32)(33)(34).…”

High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma: A population-based analysis

“…With improvements in progression-free survival in the range of 3-8 months, [6,7,16] they have become a cornerstone of therapy for metastatic RCC [1,2,17,18]. However, with that success, there has been a significant effort to utilize these therapies in the adjuvant setting for high-risk localized or locally advanced RCC.…”

“…Since then, they have become a cornerstone of RCC therapy, specifically for metastatic RCC [1]. Utilized in patients with de novo metastatic RCC or patients with metastatic progression following primary surgical management, they have been demonstrated to extend progression-free survival by 3-8 months in patients with clear-cell histology [1,2,6,7]. Their introduction has even called into question the oncologic value of cytoreductive nephrectomy, which was first established in the cytokine era [8][9][10][11].…”