Skip to main content

Renal Cell Carcinoma

  • Chapter
  • First Online:
Oncology in the Precision Medicine Era

Abstract

Multiple studies have emerged in recent years to define the biology of both clear cell and non-clear cell renal cell carcinoma (RCC). In parallel, there have been numerous pivotal trials that have introduced novel therapies for RCC. In the current chapter, we describe the intersection between these biological and clinical studies and offer a perspective on how to maximize value for patients with advanced RCC.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. The Cancer Genome Atlas Research N, Creighton CJ, Morgan M, Gunaratne PH, Wheeler DA, Gibbs RA, et al. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499:43.

    Article  Google Scholar 

  2. Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol. 2004;22(24):4991–5004.

    Article  CAS  Google Scholar 

  3. Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92.

    Article  CAS  Google Scholar 

  4. de Velasco G, Wankowicz SA, Madison R, Ali SM, Norton C, Duquette A, et al. Targeted genomic landscape of metastases compared to primary tumours in clear cell metastatic renal cell carcinoma. Br J Cancer. 2018;118(9):1238–42.

    Article  Google Scholar 

  5. Pal SK, Sonpavde G, Agarwal N, Vogelzang NJ, Srinivas S, Haas NB, et al. Evolution of circulating tumor DNA profile from first-line to subsequent therapy in metastatic renal cell carcinoma. Eur Urol. 2017;72(4):557–64.

    Article  CAS  Google Scholar 

  6. Cancer Genome Atlas Research N, Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, et al. Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med. 2016;374(2):135–45.

    Article  Google Scholar 

  7. Pal SK, Ali SM, Yakirevich E, Geynisman DM, Karam JA, Elvin JA, et al. Characterization of clinical cases of advanced papillary renal cell carcinoma via comprehensive genomic profiling. Eur Urol. 2018;73(1):71–8.

    Article  CAS  Google Scholar 

  8. Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26(3):319–30.

    Article  CAS  Google Scholar 

  9. Casuscelli J, Weinhold N, Gundem G, Wang L, Zabor EC, Drill E, et al. Genomic landscape and evolution of metastatic chromophobe renal cell carcinoma. JCI Insight. 2017;2(12).

    Google Scholar 

  10. Malouf GG, Ali SM, Wang K, Balasubramanian S, Ross JS, Miller VA, et al. Genomic characterization of renal cell carcinoma with Sarcomatoid dedifferentiation pinpoints recurrent genomic alterations. Eur Urol. 2016;70(2):348–57.

    Article  CAS  Google Scholar 

  11. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.

    Article  CAS  Google Scholar 

  12. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.

    Article  CAS  Google Scholar 

  13. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061–8.

    Article  CAS  Google Scholar 

  14. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356(22):2271–81.

    Article  CAS  Google Scholar 

  15. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet (London, England). 2008;372(9637):449–56.

    Article  CAS  Google Scholar 

  16. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26(33):5422–8.

    Article  CAS  Google Scholar 

  17. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144–50.

    Article  CAS  Google Scholar 

  18. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet (London, England). 2011;378(9807):1931–9.

    Article  CAS  Google Scholar 

  19. Zhou L, Liu XD, Sun M, Zhang X, German P, Bai S, et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016;35(21):2687–97.

    Article  CAS  Google Scholar 

  20. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917–27.

    Article  CAS  Google Scholar 

  21. Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. J Clin Oncol. 2017;35(6):591–7.

    Article  CAS  Google Scholar 

  22. Tran TA, Leong HS, Pavia-Jimenez A, Fedyshyn S, Yang J, Kucejova B, et al. Fibroblast growth factor receptor-dependent and -independent paracrine signaling by Sunitinib-resistant renal cell carcinoma. Mol Cell Biol. 2016;36(13):1836–55.

    Article  CAS  Google Scholar 

  23. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. 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):1473–82.

    Article  CAS  Google Scholar 

  24. Kwiatkowski DJ, Choueiri TK, Fay AP, Rini BI, Thorner AR, de Velasco G, et al. Mutations in TSC1, TSC2, and MTOR are associated with response to Rapalogs in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2016;22(10):2445–52.

    Article  CAS  Google Scholar 

  25. Tannir NM, Jonasch E, Albiges L, Altinmakas E, Ng CS, Matin SF, et al. Everolimus versus Sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (ESPN): a randomized multicenter phase 2 trial. Eur Urol. 2016;69(5):866–74.

    Article  CAS  Google Scholar 

  26. Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016;17(3):378–88.

    Article  CAS  Google Scholar 

  27. Choueiri TK, Plimack E, Arkenau HT, Jonasch E, Heng DYC, Powles T, et al. Biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer. J Clin Oncol. 2017;35(26):2993–3001.

    Article  CAS  Google Scholar 

  28. Schoffski P, Wozniak A, Escudier B, Rutkowski P, Anthoney A, Bauer S, et al. Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial. Eur J Cancer. 2017;87:147–63.

    Article  CAS  Google Scholar 

  29. Pal SK, Bergerot P, Dizman N, Bergerot C, Adashek J, Madison R, et al. Responses to Alectinib in ALK-rearranged papillary renal cell carcinoma. Eur Urol. 2018;74(1):124–8.

    Article  Google Scholar 

  30. Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.

    Article  CAS  Google Scholar 

  31. Motzer RJ, Penkov K, Haanen JBAG, Rini BI, Albiges L, Campbell MT, et al. LBA6_PRJAVELIN renal 101: a randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Ann Oncol. 2018;29(suppl_8):mdy424.036.

    Article  Google Scholar 

  32. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.

    Article  CAS  Google Scholar 

  33. McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24(6):749–57.

    Article  CAS  Google Scholar 

  34. Pal SK, Li SM, Wu X, Qin H, Kortylewski M, Hsu J, et al. Stool Bacteriomic profiling in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor-tyrosine kinase inhibitors. Clin Cancer Res. 2015;21(23):5286–93.

    Article  CAS  Google Scholar 

  35. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–7.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sumanta K. Pal .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dara, Y., Salgia, N., Pal, S.K. (2020). Renal Cell Carcinoma. In: Salgia, R. (eds) Oncology in the Precision Medicine Era. Springer, Cham. https://doi.org/10.1007/978-3-030-31471-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-31471-2_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-31470-5

  • Online ISBN: 978-3-030-31471-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics