Skip to main content
Log in

Targeted Anti-Cancer Therapies for Renal Cancer

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

In the past several years, significant advances in the underlying biological mechanisms of renal cell cancer, particularly the role of tumour angiogenesis, have permitted the design of molecularly targeted therapeutics. For this review, single-agent therapies inhibiting the following different targets were identified in the published literature: epithelial growth factor receptor, vascular endothelial growth factor receptor, basic fibroblast growth factor receptor, platelet-derived growth factor, nuclear factor-κβ, the mammalian target of rapamycin (mTOR) pathway, raf kinase pathway and tyrosine kinase pathway. Distinct fields of clinical research have emerged — monoclonal antibodies, small molecules, nanopeptides and immunomodulators. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed on the basis of the reported criteria for each study, and antitumour response (regression or delay in progression-free survival) ranged from 5% to 71%. On the basis of the limited studies to date, targeted therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted to further improve clinical outcome.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I

Similar content being viewed by others

References

  1. Jemal A, Murray T, Samuels A, et al. Cancer statistics. CA Cancer J Clin Mar–Apr 2006; 56(2): 106–30

    Article  Google Scholar 

  2. Mathew A, Devesa SS, Fraumeni JF Jr, et al. Global increases in kidney cancer incidence, 1973–1992. Eur J Cancer Prev 2002 Apr; 11(2): 171–8

    Article  PubMed  CAS  Google Scholar 

  3. Cohen HT, McGovern FJ. Medical progress: renal-cell carcinoma. N Engl J Med 2005; 353: 23: 2477–90

    Article  PubMed  CAS  Google Scholar 

  4. Amato RJ. Chemotherapy for renal cell carcinoma. Semin Oncol 2000; 27: 177–86

    PubMed  CAS  Google Scholar 

  5. Motzer RJ, Mazumdar M, Bacik J, et al. Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. J Clin Oncol 2000; 18: 1928–35

    PubMed  CAS  Google Scholar 

  6. Amato RJ. Thalidomide therapy for renal cell carcinoma. Crit Rev Oncol Hematol 2003; 46: 59–65

    Article  Google Scholar 

  7. Herceptin® [package insert]. South San Francisco (CA): Genentech Inc., 2002

  8. Rituxan® (rituximab) [package insert]. San Diego (CA): IDEC Pharmaceuticals Corp. and Genentech Inc., 2002

  9. Zevalin® [package insert]. San Diego (CA): IDEC Pharmaceuticals Corp., 2002

  10. Lager DJ, Slagel DD, Palechek PL. The expression of epidermal growth factor receptor and transforming growth factor alpha in renal cell carcinoma. Mod Pathol 1994; 7: 544–8

    PubMed  CAS  Google Scholar 

  11. Hofmockel G, Riess S, Bassukas ID, et al. Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact. Eur Urol 1997; 31: 478–84

    PubMed  CAS  Google Scholar 

  12. Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003; 21: 2787–99

    Article  PubMed  CAS  Google Scholar 

  13. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003; 349: 427–34

    Article  PubMed  CAS  Google Scholar 

  14. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: (23): 2335–42

    Article  PubMed  CAS  Google Scholar 

  15. Liu Z, Smyth FE, Renner C, et al. Anti-renal cell carcinoma chimeric antibody G250: cytokine enhancement of in vitro antibody-dependent cellular cytotoxicity. Cancer Immunol Immunother 2003;51: 171–7

    Google Scholar 

  16. Rowinsky EK, Schwartz GH, Gollob JA, et al. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoconal antibody inpatients with metasatic renal cell cancer. J Clin Oncol 2004; 22: 3003–15

    Article  PubMed  CAS  Google Scholar 

  17. Motzer RJ, Amato R, Todd M, et al. Phase II trial of an-tiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma. Invest New Drugs 2003; 21: 99–101

    Article  PubMed  CAS  Google Scholar 

  18. Bleumer I, Knuth A, Oosterwijk E, et al. A phase I trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients. Br J Cancer 2004; 90: 985–90

    Article  PubMed  CAS  Google Scholar 

  19. Kurzrock R, Kantarjian HM, Druker BJ, et al. Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics. Ann Intern Med 2003; 138: 819–30

    PubMed  CAS  Google Scholar 

  20. Sulzbacher I, Birner P, Traxler M, et al. Expression of platelet-derived growth factor-alpha alpha receptor is associated with tumor progression in clear cell renal cell carcinoma. Am J Clin Pathol 2003; 120: 107–12

    Article  PubMed  CAS  Google Scholar 

  21. Yamazaki K, Sakamoto M, Ohta T, et al. Overexpression of KIT in chromophobe renal cell carcinoma. Oncogene 2003; 22: 847–52

    Article  PubMed  CAS  Google Scholar 

  22. George D, Michaelson D, Oh WK, et al. Phase I study of PTK787/ZK 222584 (PTK/ZK) in metastatic renal cell carcinoma [abstract no. 1548]. Proc Am Soc Clin Oncol 2003; 22: 385

    Google Scholar 

  23. Potti A, George D. Tyrosine kinase inhibitors in renal cell carcinoma. Clin Cancer Res 2004; 10: 6371–6s

    Article  Google Scholar 

  24. Kuenen BC, Tabernero J, Baselga J, et al. Efficacy and toxicity of the angiogenesis inhibitor SU5416 as a single agent in patients with advanced renal cell carcinoma, melanoma, and soft tissue sarcoma. Clin Cancer Res 2003; 9: 1648–55

    PubMed  CAS  Google Scholar 

  25. Vuky J, Fotoohi M, Isacson C, et al. Phase II trial of imatinib mesylate (formerly known as STI-571) in patients with metastatic renal cell carcinoma (RCC) [abstract no. 1672]. Proc Am Soc Clin Oncol 2003; 22: 416

    Article  Google Scholar 

  26. Drucker B, Bacik J, Ginsberg M, et al. Phase II trial of ZD1839 (IRESSA™) in patients with advanced renal cell carcinoma. Invest New Drugs 2003; 21: 341–5

    Article  PubMed  CAS  Google Scholar 

  27. Lara PN, Quinn DI, Margolin K, et al. SU5416 plus interferon α in advanced renal cell carcinoma: a phase II California cancer consortium study with biological and imaging correlates of angiogenesis inhibition. Clin Cancer Res 2003; 9: 4772–81

    PubMed  CAS  Google Scholar 

  28. Velcade® [package insert]. Cambridge (MA): Millennium Pharmaceuticals, Inc., 2003

  29. Cusack JC. Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cancer Treat Rev 2003; 29: 21–31

    Article  PubMed  CAS  Google Scholar 

  30. Kondagunta GV, Drucker B, Schwartz L, et al. Phase II trial of bortezomib for patients with advanced renal cell carcinoma. J Clin Oncology 2004; 22(18): 3720–5

    Article  CAS  Google Scholar 

  31. Davis NB, Taber DA, Ansari RH, et al. A phase II trial of PS-341 in patients (pts) with renal cell cancer (RCC) [abstract no. 1551]. Proc Am Soc Clin Oncol 2003; 22: 386

    Article  Google Scholar 

  32. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol 2003; 3: 371–7

    Article  PubMed  CAS  Google Scholar 

  33. Atkins MB, Hidalgo M, Stadler W, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004; 22: 909–18

    Article  PubMed  CAS  Google Scholar 

  34. Gordon MS, Mendelson D, Guirguis RA, et al. ABT-510, an anti-angiogenic thrombospondin-1 (TSP-1) mimetic peptide exhibits favorable safety profile and early signals of activity in a randomized phase 1B trial [abstract no. 780]. Proc Am Soc Clin Oncol 2003; 22

  35. Amato RJ. Thalidomide: an antineoplastic agent. Curr Oncol Rep 2002; 4: 56–62

    Article  PubMed  Google Scholar 

  36. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–71

    Article  PubMed  CAS  Google Scholar 

  37. D’Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91: 4082–5

    Article  PubMed  Google Scholar 

  38. Moreira AL, Sampaio EP, Zmuidzinas A, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993; 177: 1675–80

    Article  PubMed  CAS  Google Scholar 

  39. Geitz H, Handt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996; 31: 213–21

    Article  PubMed  CAS  Google Scholar 

  40. Eisen T. Phase II results of a phase II/III study comparing thalidomide with medroxyprogesterone in patients with meta-static renal cell carcinoma [abstract no. 1606]. Proc Am Soc Clin Oncol 2003; 22: 400

    Google Scholar 

  41. Campbell SL, Khosravi-Far R, Rossman KL. Increasing complexity of Ras signaling. Oncogene 1998; 17: 1395–413

    Article  PubMed  CAS  Google Scholar 

  42. Chong H, Vikis HG, Guan KL. Mechanisms of regulating the Raf kinase family. Cell Signal 2003; 15: 463–9

    Article  PubMed  CAS  Google Scholar 

  43. Ratain, MJ, Flaherty, KT, Stalder, M, et al. Preliminary antitumor activity of BAY 43-9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase II randomized discontinuation trial (RDT) [abstract no. 4501]. ASCO Annual Meeting Proceedings. J Clinl Oncol 2004 July 15; 22 Suppl.: 14S

    Google Scholar 

  44. Escudier B, Szcylik C, Eisen T, et al. Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). 2005 ASCO Annual Meeting Proceedings. J Clin Oncol 2005 June 1; 23 16S: LBA 4510

    Google Scholar 

  45. Motzer RJ, Rini BI, Michaelson D, et al. Phase 2 trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma (RCC) [abstract no. 4508]. J Clin Oncol 2005; 23 (16S 1 Jun Suppl.): 16S

    Google Scholar 

  46. Mendel D, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2006; 9: 327–37

    Google Scholar 

  47. Motzer RJ, et al. SU011248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: results of a phase 2 trial [abstract]. Proc Am Soc Clin Oncl 2004; 23: A4500

    Google Scholar 

  48. Motzer RJ, Michaelson MD, Redman B, et al. Activity of SU 11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal carcinoma. J Clin Oncol 2006; 24: 16–24

    Article  PubMed  CAS  Google Scholar 

  49. Amato R, Misellati A, Khan M, et al. A phase II trial of RAD001 in patients (pts) with metastatic renal cell carcinoma (MRCC) [abstract no. 4530]. Proc Am Soc Clin Oncol 2006; 24(18S): 224s

    Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert J. Amato.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amato, R.J., Jac, J. Targeted Anti-Cancer Therapies for Renal Cancer. Drugs 66, 2161–2171 (2006). https://doi.org/10.2165/00003495-200666170-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200666170-00002

Keywords

Navigation