Skip to main content

Advertisement

SpringerLink
Log in

Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside

  • Clinical
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Metastatic disease occurs in a significant percentage of patients with renal cell carcinoma (RCC) and is usually associated with an overall poor prognosis. However, not all of the sites of metastases seem to have the same prognostic significance in patients receiving targeted agents. Indeed, patients with lung-only metastases seem to present a better survival than patients with other sites, whereas liver and bone metastases are associated with a worst prognosis. Some clinical studies suggest that metastatic sites are more responsive than primary tumors. This event may be due to intratumor heterogeneity in terms of somatic mutations, chromosome aberrations, and tumor gene expression, primarily centered around Von Hippel–Lindau (VHL) pathway, such as VHL mutations, HIF levels, vascular endothelial growth factor (VEGF) isoforms, and VEGF receptor levels. Nevertheless, these data do not completely explain the discordant biological behavior between primary tumor and metastatic sites. Understanding the causes of this discordance will have profound consequences on translational research and clinical trials in RCC. In this review, we overview current data on the differences between primary RCC and metastases in terms of drug target expression and clinical/radiological response to targeted agents, thus describing the prognostic role of different metastatic sites in RCC patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ljungberg, B., Cowan, N. C., Hanbury, D. C., Hora, M., Kuczyk, M. A., Merseburger, A. S., et al. (2010). EAU guidelines on renal cell carcinoma: the 2010 update. European Urology, 58, 398–406.

    Article  PubMed  Google Scholar 

  2. MacLennan, G. T., & Bostwick, D. G. (1995). Microvessel density in renal cell carcinoma: lack of prognostic significance. Urology, 46, 27–30.

    Article  CAS  PubMed  Google Scholar 

  3. Folkman, J. (1992). The role of angiogenesis in tumor growth. Semininars in Cancer Biology, 3, 65–71.

    CAS  Google Scholar 

  4. Escudier, B., Eisen, T., Stadler, W. M., Szczylik, C., Oudard, S., Siebels, M., et al. (2007). Sorafenib in advanced clear-cell renal-cell carcinoma. The New England Journal of Medicine, 356, 125–134.

    Article  CAS  PubMed  Google Scholar 

  5. Motzer, R. J., Hutson, T. E., Tomczak, P., Michaelson, D., Bukowski, R. M., Rixe, O., et al. (2007). Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. The New England Journal of Medicine, 356, 115–124.

    Article  CAS  PubMed  Google Scholar 

  6. Hudes, G., Carducci, M., Tomczak, P., Dutcher, J., Figlin, R., Kapoor, A., et al. (2007). Temsirolimus, interferon alfa, or both for advanced renal cell carcinoma. The New England Journal of Medicine, 356, 2271–2281.

    Article  CAS  PubMed  Google Scholar 

  7. Escudier, B., Pluzanska, A., Koralewski, P., Ravaud, A., Bracarda, S., Szczylik, C., et al. (2007). Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind phase III trial. The Lancet, 370, 2103–2111.

    Article  Google Scholar 

  8. Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., et al. (2008). Efficacy of everolimus in advanced renal cell carcinoma: a double-blind randomised placebo-controlled phase III trial. The Lancet, 372, 449–456.

    Article  CAS  Google Scholar 

  9. Rini, B. I., Halabi, S., Rosenberg, J. E., Stadler, W. M., Vaena, D. A., Ou, S. S., et al. (2008). Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. The Journal of Clinical Oncology, 26, 5422–5428.

    Article  CAS  Google Scholar 

  10. Sternberg, C. N., Davis, I. D., Mardiak, J., Szczylik, C., Lee, E., Wagstaff, J., et al. (2010). Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. The Journal of Clinical Oncology, 28, 1061–1068.

    Article  CAS  Google Scholar 

  11. Rini, B. I., Escudier, B., Tomczack, P., Kaprin, A., Szczylik, C., Hutson, T. E., et al. (2011). Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. The Lancet, 378, 1931–1939.

    Article  CAS  Google Scholar 

  12. Iacovelli, R., Alesini, D., Palazzo, A., Trenta, P., Santoni, M., De Marchis, L., et al. (2013). Targeted therapies and complete responses in first line treatment of metastatic renal cell carcinoma. A meta-analysis of published trials. Cancer Treatment Reviews. doi:10.1016/j.ctrv.2013.09.003.

    PubMed  Google Scholar 

  13. Flanigan, R. C., Salmon, S. E., Blumenstein, B. A., Bearman, S. I., Roy, V., McGrath, P. C., et al. (2001). Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. The New England Journal of Medicine, 345, 1655–1659.

    Article  CAS  PubMed  Google Scholar 

  14. McKay, R. R., Kroeger, N., Xie, W., Lee, J. L., Knox, J. J., Bjarnason, G. A., et al. (2013). Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. European Urology. doi:10.1016/j.eururo.2013.08.012.

    PubMed  Google Scholar 

  15. O'Dea, M. J., Zincke, H., Utz, D. C., & Bernatz, P. E. (1978). The treatment of renal cell carcinoma with solitary metastasis. The Journal of Urology, 120, 540–542.

    PubMed  Google Scholar 

  16. Kroeger, N., Choueiri, T. K., Lee, J. L., Bjarnason, G. A., Knox, J. J., Mackenzie, M. J., et al. (2013). Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy. European Urology. doi:10.1016/j.eururo.2013.07.031.

    Google Scholar 

  17. Amin, C., Wallen, E., Pruthi, R. S., Calvo, B. F., Godley, P. A., & Rathmell, W. K. (2008). Preoperative tyrosine kinase inhibition as an adjunct to debulking nephrectomy. Urology, 2008(72), 864–868.

    Article  Google Scholar 

  18. Shuch, B., Riggs, S. B., LaRochelle, J. C., Kabbinavar, F. F., Avakian, R., Pantuck, A. J., et al. (2008). Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm. The British Journal of Urology International, 102, 692–696.

    Article  Google Scholar 

  19. Thomas, A. A., Rini, B. I., Lane, B. R., Garcia, J., Dreicer, R., Klein, E. A., et al. (2009). Response of the primary tumor to neoadjuvant sunitinib in patients with advanced renal cell carcinoma. The Journal of Urology, 181, 518–523.

    Article  CAS  PubMed  Google Scholar 

  20. van der Veldt, A. A., Meijerink, M. R., van den Eertwegh, A. J., Bex, A., de Gast, G., Haanen, J. B., et al. (2008). Sunitinib for treatment of advanced renal cell cancer: primary tumor response. Clinical Cancer Research, 14, 2431–2436.

    Article  PubMed  Google Scholar 

  21. Abel, E. J., Culp, S. H., Tannir, N. M., Matin, S. F., Tamboli, P., Jonasch, E., et al. (2011). Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma. European Urology, 59, 10–15.

    Article  PubMed  Google Scholar 

  22. Zigeuner, R., Ratschek, M., Rehak, P., Schips, L., & Langner, C. (2004). Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue. Urology, 63, 651–655.

    Article  PubMed  Google Scholar 

  23. Aziz, S. A., Sznol, J., Adeniran, A., Colberg, J. W., Camp, R. L., & Kluger, H. M. (2013). Vascularity of primary and metastatic renal cell carcinoma specimens. Journal of Translational Medicine, 11, 15.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., et al. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. The New England Journal of Medicine, 366, 883–892.

    Article  CAS  PubMed  Google Scholar 

  25. Xu, X., Hou, Y., Yin, X., Bao, L., Tang, A., Song, L., et al. (2012). Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell, 148, 886–895.

    Article  CAS  PubMed  Google Scholar 

  26. Aziz, S. A., Sznol, J. A., Adeniran, A., Parisi, F., Kluger, Y., Camp, R. L., et al. (2013). Expression of drug targets in primary and matched metastatic renal cell carcinoma tumors. BMC Clinical Pathology, 13, 3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Abou Youssif, T., Fahmy, M. A., Koumakpayi, I. H., Ayala, F., Al Marzooqi, S., Chen, G., et al. (2011). The mammalian target of rapamycin pathway is widely activated without PTEN deletion in renal cell carcinoma metastases. Cancer, 117, 290–300.

    Article  CAS  PubMed  Google Scholar 

  28. Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., et al. (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European Journal of Cancer, 45, 228–247.

    Article  CAS  PubMed  Google Scholar 

  29. Nishino, M., Jagannathan, J. P., Krajewski, K. M., O'Regan, K., Hatabu, H., Shapiro, G., et al. (2012). Personalized tumor response assessment in the era of molecular medicine: cancer specific and therapy-specific response criteria to complement pitfalls of RECIST. AJR. American Journal of Roentgenology, 198, 737–745.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Baccala, A., Hedfepeth, R., Kaouk, J., Magi-Galluzzi, C., Gilligan, T., & Fergany, A. (2007). Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib. International Journal of Urology, 14, 1095–1097.

    Article  PubMed  Google Scholar 

  31. Han, K. S., Jung, D. C., Choi, H. J., Jeong, M. S., Cho, K. S., Joung, J. Y., et al. (2010). Pretreatment assessment of tumor enhancement on contrast-enhanced computed tomography as a potential predictor of treatment outcome in metastatic renal cell carcinoma patients receiving antiangiogenic therapy. Cancer, 116, 2332–2342.

    CAS  PubMed  Google Scholar 

  32. Schwartz, L. H., Mazumdar, M., Wang, L., Smith, A., Marion, S., Panicek, D. M., et al. (2003). Response assessment classification in patients with advanced renal cell carcinoma treated on clinical trials. Cancer, 98, 1611–1619.

    Article  PubMed  Google Scholar 

  33. Derwinger, K., Kodeda, K., & Gerjy, R. (2010). Age aspects of demography, pathology and survival assessment in colorectal cancer. Anticancer Research, 30, 5227–5231.

    PubMed  Google Scholar 

  34. Beck, S. D., Patel, M. I., Snyder, M. E., Kattan, M. W., Motzer, R. J., Reuter, V. E., et al. (2004). Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma. Annals of Surgical Oncology, 11, 71–77.

    Article  PubMed  Google Scholar 

  35. Renshaw, A. A., & Richie, J. P. (1999). Subtypes of renal cell carcinoma: different onset and sites of metastatic disease. Am Journal of Clinical Patholology, 111, 539–543.

    CAS  Google Scholar 

  36. Snow, R. M., & Schellhammer, P. F. (1982). Spontaneous regression of metastatic renal cell carcinoma. Urology, 20, 177–181.

    Article  CAS  PubMed  Google Scholar 

  37. López-Lago, M. A., Posner, S., Thodima, V. J., Molina, A. M., Motzer, R. J., & Chaganti, R. S. (2012). Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic response during renal cell carcinoma progression. Oncogene. doi:10.1038/onc.2012.201.

    PubMed Central  PubMed  Google Scholar 

  38. Merimsky, O., Gez, E., Weitzen, R., Nehushtan, H., Rubinov, R., Hayat, H., et al. (2004). Targeting pulmonary metastases of renal cell carcinoma by inhalation of interleukin-2. Annals of Oncology, 15, 610–612.

    Article  CAS  PubMed  Google Scholar 

  39. Bianchi, M., Sun, M., Jeldres, C., Shariat, S. F., Trinh, Q. D., Briganti, A., et al. (2012). Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Annals of Oncology, 23, 973–980.

    Article  CAS  PubMed  Google Scholar 

  40. Fidler, I. J. (2003). The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nature Reviews Cancer, 3, 453–458.

    Article  CAS  PubMed  Google Scholar 

  41. Woodward, E., Jagdev, S., McParland, L., Clark, K., Gregory, W., Newsham, A., et al. (2001). Skeletal complications and survival in renal cancer patients with bone metastases. Bone, 48, 160–166.

    Article  Google Scholar 

  42. Kominsky, S. L., Doucet, M., Brady, K., & Weber, K. L. (2007). TGF-beta promotes the establishment of renal cell carcinoma bone metastasis. Journal of Bone and Mineral Research, 22, 37–44.

    Article  CAS  PubMed  Google Scholar 

  43. Weber, K., Doucet, M., & Kominsky, S. (2007). Renal cell carcinoma bone metastasis-elucidating the molecular targets. Cancer and Metastasis Reviews, 26, 691–704.

    Article  PubMed  Google Scholar 

  44. Beuselinck, B., Oudard, S., Rixe, O., Wolter, P., Blesius, A., Ayllon, J., et al. (2011). Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Annals of Oncology, 22, 794–800.

    Article  CAS  PubMed  Google Scholar 

  45. Choueiri, T., Garcia, J. A., Elson, P., Khasawneh, M., Usman, S., Golshayan, A. R., et al. (2007). Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer, 110, 543–550.

    Article  CAS  PubMed  Google Scholar 

  46. Riechelmann, R. P., Chin, S., Wang, L., Tannock, I. F., Berthold, D. R., Moore, M. J., et al. (2008). Sorafenib for metastatic renal cancer: the Princess Margaret experience. American Journal of Clinical Oncology, 31, 182–187.

    Article  CAS  PubMed  Google Scholar 

  47. Santini, D., Procopio, G., Porta, C., Ibrahim, T., Barni, S., Mazzara, C., et al. (2013). Natural history of malignant bone disease in renal cancer: final results of an Italian Bone Metastasis Survey. PLOSONE (in press).

  48. Zolnierek, J., Nurzynski, P., Langiewicz, P., Oborska, S., Waśko-Grabowska, A., Kuszatal, E., et al. (2010). Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases. Journal of Cancer Research and Clinical Oncology, 136, 371–378.

    Article  CAS  PubMed  Google Scholar 

  49. Maita, S., Yuasa, T., Tsuchiya, N., Mitobe, Y., Narita, S., Horikawa, Y., et al. (2012). Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function. International Journal of Cancer, 130, 677–684.

    Article  CAS  Google Scholar 

  50. Keizman, D., Ish-Shalom, M., Pili, R., Hammers, H., Eisenberger, M. A., Sinibaldi, V., et al. (2012). Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma. European Journal of Cancer, 48, 1031–1037.

    Article  CAS  PubMed  Google Scholar 

  51. Beuselinck, B., Wolter, P., Karadimou, A., Elaidi, R., Dumez, H., Rogiers, A., et al. (2012). Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinoma with bone metastases. British Journal of Cancer, 107, 1665–1671.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Kneissel, M., Luong-Nguyen, N. H., Baptist, M., Cortesi, R., Zumstein-Mecker, S., Kossida, S., et al. (2004). Everolimus suppresses cancellous bone loss, bone resorption, and cathepsin K expression by osteoclasts. Bone, 35, 1144–1156.

    Article  CAS  PubMed  Google Scholar 

  53. Sugatani, T., & Hruska, K. A. (2005). Akt1/Akt2 and mammalian target of rapamycin/Bim play critical roles in osteoclast differentiation and survival, respectively, whereas Akt is dispensable for cell survival in isolated osteoclast precursors. The Journal of Biological Chemistry, 280, 3583–3589.

    Article  CAS  PubMed  Google Scholar 

  54. Hussein, O., Tiedemann, K., Murshed, M., & Komarova, S. V. (2012). Rapamycin inhibits osteolysis and improves survival in a model of experimental bone metastases. Cancer Letters, 314, 176–184.

    Article  CAS  PubMed  Google Scholar 

  55. Okui, T., Shimo, T., Fukazawa, T., Kurio, N., Hassan, N. M., Honami, T., et al. (2010). Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction. Molecular Cancer Therapeutics, 9, 2960–2969.

    Article  CAS  PubMed  Google Scholar 

  56. Kassabinn, A., Stein, J., Jabbour, N., Parsa, K., Skinner, D., Parekh, D., et al. (2000). Renal cell carcinoma metastatic to the pancreas: a single-institution series and review of the literature. Adult Urology, 56(211–215), 2000.

    Google Scholar 

  57. Shah, S., & Mortele, K. J. (2007). Uncommon solid pancreatic neoplasms: ultrasound, computed tomography, magnetic resonance imaging features. Seminars in Ultrasound, CT, and MR, 28, 357–370.

    Article  PubMed  Google Scholar 

  58. Ballarin, R., Spaggiari, M., Cautero, N., De Ruvo, N., Montalti, R., Longo, C., et al. (2011). Pancreatic metastases from renal cell carcinoma: the state of the art. World Journal of Gastroenterology, 17, 4747–4756.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Wente, M. N., Kleeff, J., Esposito, I., Hartel, M., Müller, M. W., Fröhlich, B. E., et al. (2005). Renal cancer cell metastasis into the pancreas. Pancreas, 30, 218–222.

    Article  PubMed  Google Scholar 

  60. Medioni, J., Choueiri, T. K., Zinzindohouè, F., Cho, D., Fournier, L., Oudard, S., et al. (2009). Response of renal cell carcinoma pancreatic metastasis to sunitinib treatment: a retrospective analysis. The Journal of Urology, 181, 2470–2475.

    Article  CAS  PubMed  Google Scholar 

  61. Grassi, P., Verzoni, E., Mariani, L., De Braud, F., Coppa, J., Mazzaferro, V., et al. (2013). Prognostic role of pancreatic metastases from renal cell carcinoma: results from an Italian Center. Clinical Genitourinary Cancer. doi:10.1016/j.clgc.2013.04.022.

    PubMed  Google Scholar 

  62. Sheehan, J. P., Sun, M. H., Kondziolka, D., Flickinger, J., & Lunsford, L. D. (2003). Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. Journal of Neurosurgery, 98, 342–349.

    Article  PubMed  Google Scholar 

  63. Delattre, J. Y., Krol, G., Thaler, H. T., & Posner, J. B. (1988). Distribution of brain metastases. Archives of Neurology, 45, 741–744.

    Article  CAS  PubMed  Google Scholar 

  64. Wronski, M., Maor, M. H., Davis, B. J., Sawaya, R., & Levin, V. A. (1997). External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center. International Journal of Radiation Oncology, Biology, Physics, 37, 753–759.

    Article  CAS  PubMed  Google Scholar 

  65. Cannady, S. B., Cavanaugh, K. A., Lee, S. Y., Bukowski, R. M., Olencki, T. E., Stevens, G. H., et al. (2004). Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study. International Journal of Radiation Oncology, Biology, Physics, 58, 253–258.

    Article  PubMed  Google Scholar 

  66. Culine, S., Bekradda, M., Kramar, A., Rey, A., Escudier, B., & Droz, J. P. (1998). Prognostic factors for survival in patients with brain metastases from renal cell carcinoma. Cancer, 83, 2548–2553.

    Article  CAS  PubMed  Google Scholar 

  67. Gore, M. E., Hariharan, S., Porta, C., Bracarda, S., Hawkins, R., Bjarnason, G. A., et al. (2011). Sunitinib in metastatic renal cell carcinoma patients with brain metastases. Cancer, 117, 501–509.

    Article  CAS  PubMed  Google Scholar 

  68. Stadler, W. M., Figlin, R. A., McDermott, D. F., Dutcher, J. P., Knox, J. J., Miller, W. H., Jr., et al. (2010). Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer, 116, 1272–1280.

    Article  CAS  PubMed  Google Scholar 

  69. Vanhuyse, M., Penel, N., Caty, A., Fumagalli, I., Alt, M., Zini, L., et al. (2012). Do anti-angiogenic therapies prevent brain metastases in advanced renal cell carcinoma? Bulletin du Cancer, 99, 100–106.

    PubMed  Google Scholar 

  70. Verma, J., Jonasch, E., Allen, P., Tannir, N., & Mahajan, A. (2011). Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer, 117, 4958–4965.

    Article  CAS  PubMed  Google Scholar 

  71. Verma, J., Jonasch, E., Allen, P. K., Weinberg, J. S., Tannir, N., Chang, E. L., et al. (2012). The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma. American Journal of Clinical Oncology, 36(6), 620–624.

    Article  CAS  Google Scholar 

  72. Dudek, A. Z., Raza, A., Chi, M., Singhal, M., Oberoi, R., Mittapalli, R. K., et al. (2013). Brain metastases from renal cell carcinoma in the era of tyrosine kinase inhibitors. Clinical Genitourinary Cancer, 11, 155–160.

    Article  PubMed  Google Scholar 

  73. Cochran, D. C., Chan, M. D., Aklilu, M., Lovato, J. F., Alphonse, N. K., Bourland, J. D., et al. (2012). The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery. Journal of Neurosurgery, 116, 978–983.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Fukata, S., Inoue, K., Kamada, M., Kawada, C., Furihata, M., Ohtsuki, Y., et al. (2005). Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma. Cancer, 103, 931–942.

    Article  CAS  PubMed  Google Scholar 

  75. Van der Veldt, A. A. M., Meijerink, M. R., Van der Eertwegh, A. J. M., Haanen, J. B., Boven, E., et al. (2010). Choi response criteria for early prediction of clinical outcome in patients with metastatic renal cell cancer treated with sunitinib. British Journal of Cancer, 102, 803–809.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Schmidt, N., Hess, V., Zumbrunn, T., Rothermundt, C., Bongartz, G., & Potthast, S. (2013). Choi response criteria for prediction of survival in patients with metastatic renal cell carcinoma treated with anti-angiogenic therapies. European Radiology, 23, 632–639.

    PubMed  Google Scholar 

  77. Smith, A. D., Leiber, M. L., & Shah, S. N. (2010). Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast-enhanced CT. AJR. American Journal of Roentgenology, 194, 157–165.

    Article  PubMed  Google Scholar 

  78. Thiam, R., Fournier, L. S., Trinquart, L., Medioni, J., Chatellier, G., Balvay, D., et al. (2010). Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib. Annals of Oncology, 21, 936–941.

    Article  CAS  PubMed  Google Scholar 

  79. Krajewski, K. M., Guo, M., Van der Abbeele, A. D., Yap, J., Ramaiya, N., Jagannathan, J., et al. (2011). Comparison of four early post therapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. European Urology, 59, 856–862.

    Article  PubMed  Google Scholar 

  80. Oudard, S., Thiam, R., Fournier, L. S., Medioni, J., Lamuraglia, M., Scotte, F., et al. (2012). Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: Analysis of response and progression-free survival in the RECORD-1 study. European Journal of Cancer, 48, 1512–1528.

    Article  CAS  PubMed  Google Scholar 

  81. Smith, A. D., Shah, S. N., Rini, B. I., Lieber, M. L., Remer, E. M., et al. (2010). Morphology, attenuation, size and structure (MASS) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. AJR. American Journal of Roentgenology, 194, 1470–1478.

    Article  PubMed  Google Scholar 

  82. Hittinger, M., Staehler, M., Schramm, N., Ubleis, C., Becker, C., Reiser, M., et al. (2012). Course of size and density of metastatic renal cell carcinoma lesions in the early follow-up of molecular targeted therapy. Urologic Oncology, 30, 695–703.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare to have no conflicts of interest.

Author information

Authors and Affiliations

  1. Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126, Ancona, Italy

    Matteo Santoni, Luciano Burattini & Stefano Cascinu

  2. Department of Medical Oncology, University Campus Bio-Medico Roma, Oncologia Medica, Rome, Italy

    Daniele Santini

  3. Medical Oncology, “G.B. Rossi” Academic Hospital, University of Verona, Verona, Italy

    Francesco Massari & Giampaolo Tortora

  4. Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Clinica di Urologia, Polytechnic University of the Marche Region, via Conca 71, 60126, Ancona, Italy

    Alessandro Conti

  5. Department of Medical Oncology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy

    Roberto Iacovelli

  6. Division of Pancreatic and Digestive Surgery, Polytechnic University of the Marche Region, via Conca 71, 60126, Ancona, Italy

    Massimo Falconi

  7. Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy

    Rodolfo Montironi

Authors
  1. Matteo Santoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniele Santini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco Massari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandro Conti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto Iacovelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luciano Burattini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giampaolo Tortora
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Massimo Falconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rodolfo Montironi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stefano Cascinu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matteo Santoni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santoni, M., Santini, D., Massari, F. et al. Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside. Cancer Metastasis Rev 33, 321–331 (2014). https://doi.org/10.1007/s10555-013-9453-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-013-9453-5

Keywords

Search

Navigation