Treatment Strategies for Clear Cell Renal Cell Carcinoma: Past, Present and Future

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Apr 7

PMID 37025584

Authors

Junwei Yang

Kuansong Wang

Zhichun Yang

Affiliations

Soon will be listed here.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, which is prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy. The burden it places on human health due to its refractory nature and rising incidence rate is substantial. Researchers have recently determined the ccRCC risk factors and optimized the clinical therapy based on the disease's underlying molecular mechanisms. In this paper, we review the established clinical therapies and novel potential therapeutic approaches for ccRCC, and we support the importance of investigating novel therapeutic options in the context of combining established therapies as a research hotspot, with the goal of providing diversified therapeutic options that promise to address the issue of drug resistance, with a view to the early realization of precision medicine and individualized treatment.

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References

Xiao W, Xiong Z, Xiong W, Yuan C, Xiao H, Ruan H . Melatonin/PGC1A/UCP1 promotes tumor slimming and represses tumor progression by initiating autophagy and lipid browning. J Pineal Res. 2019; 67(4):e12607. DOI: 10.1111/jpi.12607. View

Lo K, Sun L . Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes. Biosci Rep. 2013; 33(5). PMC: 3764508. DOI: 10.1042/BSR20130046. View

Choueiri T, Pal S, McDermott D, Morrissey S, Ferguson K, Holland J . A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Ann Oncol. 2014; 25(8):1603-8. PMC: 6279111. DOI: 10.1093/annonc/mdu184. View

Hu-Lowe D, Zou H, Grazzini M, Hallin M, Wickman G, Amundson K . Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008; 14(22):7272-83. DOI: 10.1158/1078-0432.CCR-08-0652. View

Choueiri T, Bauer T, Papadopoulos K, Plimack E, Merchan J, Mcdermott D . Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021; 27(5):802-805. PMC: 9128828. DOI: 10.1038/s41591-021-01324-7. View

Sim G, Radvanyi L . The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 2014; 25(4):377-90. DOI: 10.1016/j.cytogfr.2014.07.018. View

Schodel J, Grampp S, Maher E, Moch H, Ratcliffe P, Russo P . Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer. Eur Urol. 2015; 69(4):646-657. PMC: 5012644. DOI: 10.1016/j.eururo.2015.08.007. View

Xiong Z, Xiao W, Bao L, Xiong W, Xiao H, Qu Y . Tumor Cell "Slimming" Regulates Tumor Progression through PLCL1/UCP1-Mediated Lipid Browning. Adv Sci (Weinh). 2019; 6(10):1801862. PMC: 6523368. DOI: 10.1002/advs.201801862. View

Agarwal Y, Milling L, Chang J, Santollani L, Sheen A, Lutz E . Intratumourally injected alum-tethered cytokines elicit potent and safer local and systemic anticancer immunity. Nat Biomed Eng. 2022; 6(2):129-143. PMC: 9681025. DOI: 10.1038/s41551-021-00831-9. View

10.

Choueiri T, Powles T, Burotto M, Escudier B, Bourlon M, Zurawski B . Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. PMC: 8436591. DOI: 10.1056/NEJMoa2026982. View

11.

Motzer R, Hutson T, Glen H, Michaelson M, Molina A, Eisen T . Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015; 16(15):1473-1482. DOI: 10.1016/S1470-2045(15)00290-9. View

12.

Abbas A, Trotta E, Simeonov D, Marson A, Bluestone J . Revisiting IL-2: Biology and therapeutic prospects. Sci Immunol. 2018; 3(25). DOI: 10.1126/sciimmunol.aat1482. View

13.

Motzer R, Escudier B, Tomczak P, Hutson T, Michaelson M, Negrier S . Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013; 14(6):552-62. DOI: 10.1016/S1470-2045(13)70093-7. View

14.

Motzer R, Escudier B, Mcdermott D, George S, Hammers H, Srinivas S . Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1803-13. PMC: 5719487. DOI: 10.1056/NEJMoa1510665. View

15.

Hahn A, Drake C, Denmeade S, Zakharia Y, Maughan B, Kennedy E . A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma. Oncologist. 2020; 25(2):121-e213. PMC: 7011628. DOI: 10.1634/theoncologist.2019-0599. View

16.

Motzer R, Hutson T, Cella D, Reeves J, Hawkins R, Guo J . Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013; 369(8):722-31. DOI: 10.1056/NEJMoa1303989. View

17.

McGregor B, Gordon M, Flippot R, Agarwal N, George S, Quinn D . Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced renal cell carcinoma. Invest New Drugs. 2020; 38(6):1807-1814. PMC: 7578086. DOI: 10.1007/s10637-020-00945-y. View

18.

Fendler A, Bauer D, Busch J, Jung K, Wulf-Goldenberg A, Kunz S . Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients. Nat Commun. 2020; 11(1):929. PMC: 7026425. DOI: 10.1038/s41467-020-14700-7. View

19.

Moreno-Smith M, Lakoma A, Chen Z, Tao L, Scorsone K, Schild L . p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy. Clin Cancer Res. 2017; 23(21):6629-6639. PMC: 5959272. DOI: 10.1158/1078-0432.CCR-17-0668. View

20.

Motzer R, Alekseev B, Rha S, Porta C, Eto M, Powles T . Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021; 384(14):1289-1300. DOI: 10.1056/NEJMoa2035716. View