Novel Targeted Therapies for Renal Cell Carcinoma: Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition

Renée Maria Saliby; Eddy Saad; Chris Labaki; Wenxin Xu; David A Braun; Srinivas R Viswanathan; Ziad Bakouny

doi:10.1016/j.hoc.2023.05.022

Novel Targeted Therapies for Renal Cell Carcinoma: Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition

Hematol Oncol Clin North Am. 2023 Oct;37(5):1015-1026. doi: 10.1016/j.hoc.2023.05.022. Epub 2023 Jun 28.

Authors

Renée Maria Saliby¹, Eddy Saad², Chris Labaki³, Wenxin Xu⁴, David A Braun⁵, Srinivas R Viswanathan⁶, Ziad Bakouny⁷

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, 300 George Street, Suite 6400, New Haven, CT 06510, USA.
² Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA.
⁵ Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, 300 George Street, Suite 6400, New Haven, CT 06510, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA. Electronic address: srinivas.viswanathan@dfci.harvard.edu.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. Electronic address: ziad_elbakouny@dfci.harvard.edu.

PMID: 37385938
DOI: 10.1016/j.hoc.2023.05.022

Abstract

Targeted therapies have revolutionized the treatment of renal cell carcinoma (RCC). The VHL/HIF pathway is responsible for the regulation of oxygen homeostasis and is frequently altered in RCC. Targeting this pathway as well as the mTOR pathway have yielded remarkable advances in the treatment of RCC. Here, we review the most promising novel targeted therapies for the treatment of RCC, including HIF2α, MET, metabolic targeting, and epigenomic reprogramming.

Keywords: CDK4/6 inhibitors; Clear cell RCC; Glutaminase inhibitors; HIF2α inhibitors; Renal cell carcinoma; Targeted therapy; Tyrosine kinase inhibitors; Variant histology RCC.

Publication types

Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Carcinoma, Renal Cell* / drug therapy
Carcinoma, Renal Cell* / genetics
Carcinoma, Renal Cell* / metabolism
Humans
Kidney Neoplasms* / drug therapy
Kidney Neoplasms* / metabolism
Kidney Neoplasms* / pathology
TOR Serine-Threonine Kinases
Vascular Endothelial Growth Factor A

Substances

Vascular Endothelial Growth Factor A
TOR Serine-Threonine Kinases

Grants and funding

P30 CA016359/CA/NCI NIH HHS/United States