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Current and Emerging Therapeutic Targets for Metastatic Renal Cell Carcinoma

  • Kevin Zarrabi
  • Shenhong Wu
Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Genitourinary Cancers

Abstract

Purpose of review

The treatment of advanced renal cell carcinoma has evolved dramatically over recent years. In this review, we will summarize current and emerging therapies based on molecular targets and provide insight into treatment strategy for metastatic renal cell carcinoma.

Recent findings

We have witnessed a paradigm shift in the therapeutic landscape as treatment was formerly reliant on cytokine-based agents which have now been replaced with therapies targeting angiogenesis, mammalian target of rapamycin pathways, and immune responses. These dramatic changes are primarily due to our improved understanding of the underlying mutations and molecular mechanisms leading to tumorigenesis and progression.

Summary

We now have targeted agents in the form of small-molecule tyrosine kinase inhibitors, monoclonal antibodies, and mTOR inhibitors. Moreover, immunotherapy-targeting checkpoints of T-lymphocyte activity has provided increased overall survival and a new class of agents with potential to radically change the treatment options. With these agents and their combination, durable responses are increasingly seen even though treatment resistance remains a huge challenge. New treatment strategies are rapidly developing and the therapeutic landscape is expected for further evolution.

Keywords

Renal cell carcinoma Targeted therapy Immunotherapy 

Abbreviations

RCC

renal cell carcinoma

TKI

tyrosine kinase inhibitor

mRCC

metastatic renal cell carcinoma

HDIL-2

high-dose interleukin-2

IFN-α

interferon-alpha

VEGF

vascular endothelial growth factor

PDGF

platelet-derived growth factor

mTOR

mammalian target of rapamycin

PFS

progression-free survival

OS

overall survival

NCCN

National Comprehensive Cancer Network

mPFS

median progression free survival

AXL

anexelekto

MET

mesenchymal epithelial transition

ORR

objective response rate

mAB

monoclonal antibody

FGFR

fibroblast growth factor receptor

NSCLC

non-small cell lung cancer

HRQoL

health-related quality of life

TAMs

tumor-associated macrophages

TVs

tumor vaccines

ALK

activin receptor-like kinase 1

Notes

Authors’ Contributions

KZ and SW contributed to the data collection, data analysis, and writing of the manuscript.

Funding

This report required no funding.

Compliance with Ethical Standards

Conflict of Interest

Kevin Zarrabi declares that he has no conflict of interest.

Shenhong Wu has served as a speaker for Exelixis, Novartis, and Pfizer.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineStony Brook University HospitalStony BrookUSA
  2. 2.Division of Hematology/Oncology, Department of MedicineNorthport VA Medical CenterNorthportUSA

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