nach oben

Cancer and Metastasis Reviews

Erschienen in:

01.12.2014 | Clinical

Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art

verfasst von: J. Michael Randall, Frederick Millard, Razelle Kurzrock

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

Renal cell carcinoma (RCC) is among the most prevalent malignancies in the USA. Most RCCs are sporadic, but hereditary syndromes associated with RCC account for 2–3 % of cases and include von Hippel-Lindau, hereditary leiomyomatosis, Birt-Hogg-Dube, tuberous sclerosis, hereditary papillary RCC, and familial renal carcinoma. In the past decade, our understanding of the genetic mutations associated with sporadic forms of RCC has increased considerably, with the most common mutations in clear cell RCC seen in the VHL, PBRM1, BAP1, and SETD2 genes. Among these, BAP1 mutations are associated with aggressive disease and decreased survival. Several targeted therapies for advanced RCC have been approved and include sunitinib, sorafenib, pazopanib, axitinib (tyrosine kinase inhibitors (TKIs) with anti-vascular endothelial growth factor (VEGFR) activity), everolimus, and temsirolimus (TKIs that inhibit mTORC1, the downstream part of the PI3K/AKT/mTOR pathway). High-dose interleukin 2 (IL-2) immunotherapy and the combination of bevacizumab plus interferon-α are also approved treatments. At present, there are no predictive genetic markers to direct therapy for RCC, perhaps because the vast majority of trials have been evaluated in unselected patient populations, with advanced metastatic disease. This review will focus on our current understanding of the molecular genetics of RCC, and how this may inform therapeutics.

Siegel, R., Naishadham, D., & Jemal, A. (2012). Cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 62, 10–29.

Cohen, H. T., & McGovern, F. (2005). Renal-cell carcinoma. New England Journal of Medicine, 353, 2477–2490.PubMed

Lopez-Beltran, A., Carrasco, J. C., Cheng, L., Scarpelli, M., Kirkali, Z., & Montironi, R. (2009). 2009 update on the classification of renal epithelial tumors in adults. International Journal of Urology, 16, 432–443.PubMed

Albiges, L., Molinie, V., & Escudier, B. (2012). Non-clear cell renal cell carcinoma: does the mammalian target of rapamycin represent a rational therapeutic target? The Oncologist, 17, 1051–1062.PubMedCentralPubMed

Rini, B. I., Campbell, S. C., & Escudier, B. (2009). Renal cell carcinoma. Lancet, 373, 1119–1132.PubMed

Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., et al. (2011). COSMIC: mining complete cancer genomes in the catalogue of somatic mutations in cancer. Nucleic Acids Research, 39, D945–D950. doi:10.1093/nar/gkq929.PubMedCentralPubMed

Nickerson, M. L., Jaeger, E., Yangu, S., Dorocher, J. A., Mahurakar, S., Zaridze, D., et al. (2008). Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clinical Cancer Research, 14, 4726–4734.PubMedCentralPubMed

Kim, W. Y., & Kaelin, W. G. (2004). Role of VHL gene mutation in human cancer. Journal of Clinical Oncology, 22, 4991–5004.PubMed

Varela, I., Tarpey, P., Raine, K., Huang, D., Ong, C. K., Stephens, P., et al. (2011). Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal cell carcinoma. Nature, 469, 539–542.PubMedCentralPubMed

10.

Duns, G., Hofstra, R. M., Sietzema, J. G., Hollema, H., vanDuivenbode, I., Kuik, A., et al. (2012). Targeted exome sequencing in clear cell renal cell carcinoma tumors suggests aberrant chromatin regulation as a crucial step in ccRCC development. Human Mutation, 33, 1059–1062.PubMed

11.

Hakimi, A. A., Ostrovnaya, I., Reva, B., Schultz, N., Chen, Y.-B., Gonen, M., et al. (2013). Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network. Clinical Cancer Research. doi:10.1158/1078-0432.CCR-12-3886.PubMedCentralPubMed

12.

Pena-Llopis, S., Vega-Rubin-de-Celis, S., Liao, A., Leng, N., Pavia-Jimenez, A., Wang, S., et al. (2012). BAP1 loss defines a new class of renal cell carcinoma. Nature Genetics, 44, 751–759.PubMedCentralPubMed

13.

Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., et al. (2010). Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 463, 360–363.PubMedCentralPubMed

14.

Hakimi, A. A., Chen, Y.-B., Wren, J., Gonen, M., Abdel-Wahab, O., Heguy, A., et al. (2013). Clinical and pathologic impact of select chromatin-modulating tumor suppressors in clear cell renal cell carcinoma. European Urology, 63, 848–854.PubMedCentralPubMed

15.

Duns, G., van den Berg, E., van Duivenbode, I., Osinga, J., Hollema, H., Hofstra, R. M., et al. (2010). Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. Cancer Research, 70, 4287–4291.PubMed

16.

Guo, G., Gui, Y., Gao, S., Tang, A., Hu, X., Huang, Y., et al. (2012). Frequent mutation of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nature Genetics, 44, 17–19.

17.

Zhang, X., Xu, R., Zhu, B., Yang, X., Ding, X., Duan, S., et al. (2007). Syne-1 and Syne-2 play crucial roles in myonuclear anchorage and motor neuron innervation. Development, 134, 901–908.PubMed

18.

Muller, P. A. J., & Vousden, K. H. (2013). p53 mutations in cancer. Nature Cell Biology, 15, 2–8.PubMed

19.

Niu, X., Zhang, T., Liao, L., Zhou, L., Linder, D., Zhou, M., et al. (2012). The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C. Oncogene, 31, 776–786.PubMedCentralPubMed

20.

Li, W.-D., Li, Q. R., Xu, S. N., Wei, F. J., Ye, Z. J., Cheng, J. K., et al. (2013). Exome sequencing identifies an MLL3 gene germ line mutation in a pedigree of colorectal cancer and acute myeloid leukemia. Blood, 121, 1478–1479.PubMed

21.

Liu, P., Morrison, C., Wang, L., Xiong, D., Vedell, P., Cui, P., et al. (2012). Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing. Carcinogenesis, 33, 1270–1276.PubMedCentralPubMed

22.

Mayers, C. M., Wadell, J., McLean, K., Venere, M., Malik, M., Shibata, T., et al. (2010). The rho guanine nucleotide exchange factor AKAP13 (BRX) is essential for cardiac development in mice. Journal of Biological Chemistry, 285, 12344–12354.PubMedCentralPubMed

23.

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.PubMed

24.

Shankar, J., Messenberg, A., Chan, J., Underhill, T. M., Foster, L. J., & Nabi, I. R. (2010). Pseudopodial actin dynamics control epithelia-mesenchymal transition in metastatic cancer cells. Cancer Research, 70, 3780–3790.PubMed

25.

Berghs, S., Aggujaro, D., Dirkx, R., Maksimova, E., Stabach, P., Hermel, J. M., et al. (2000). Beta IV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in central and peripheral nervous system. Journal of Cell Biology, 151, 985–1002.PubMedCentralPubMed

26.

Robinson, R., Carpenter, D., Shaw, M.-A., Halsall, J., & Hopkins, P. (2006). Mutation in RYR1 in malignant hyperthermia and central core disease. Human Mutation, 27, 977–989.PubMed

27.

Carlsson, E., Ranki, A., Sipila, L., Karenko, L., Abdel-Rahman, W., Ovaska, K., et al. (2012). Potential role of a navigator gene NAV3 in colorectal cancer. British Journal of Cancer, 106, 517–524.PubMedCentralPubMed

28.

Lamason, R., McCully, R., Lew, S., & Pomerantz, J. (2010). Oncogenic CARD11 mutation induce hyperactive signaling by disrupting autoinhibition by the PKC-responsive inhibitory domain. Biochemistry, 38, 8240–8250.

29.

Gandhi, P. N., Chen, S. G., & Wilson-Delfosse, A. L. (2009). Leucine-rich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson’s disease. Journal of Neuroscience Research, 87, 1283–1295.PubMedCentralPubMed

30.

Sansal, I., & Sellers, W. R. (2004). The biology and clinical relevance of the PTEN tumor suppressor pathway. Journal of Clinical Oncology, 22, 2954–2963.PubMed

31.

Guo, C., Chang, C.-C., Wortham, M., Chen, L. H., Kernagis, D. H., Qin, X., et al. (2012). Global indentification of MLL2-targeted local reveals MLL2’s role in diverse signaling pathways. Proceedings of the National Academy of Sciences of the United States of America, 109, 17603–17608.PubMedCentralPubMed

32.

Karakas, B., Bachman, K., & Park, B. (2006). Mutation of the PIK3CA oncogene in human cancers. British Journal of Cancer, 94, 455–459.PubMedCentralPubMed

33.

Lee, J., & Paull, T. (2007). Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene, 26, 7741–7748.PubMed

34.

Sehrawat, S., Emandez, T., Culler, X., Takahashi, M., Ono, Y., Komarova, Y., et al. (2011). AKAP9 regulation of microtubule dynamics promotes Epac-1 induced endothelial barrier properties. Blood, 117, 708–718.PubMedCentralPubMed

35.

Walters, J. T. R., Corvin, A., Owen, M. J., Williams, H., Dragovic, M., Quinn, E. M., et al. (2010). Psychosis susceptibility gene ZNF804A and cognitive performance in schizophrenia. Archives of General Psychiatry, 67, 692–700.PubMed

36.

Huang, J., & Manning, B. D. (2008). The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochemistry Journal, 412, 179–190.

37.

Sato, D., Lionel, A. C., Leblond, C. S., Prasad, A., Pinto, D., Walker, S., et al. (2012). SHANK1 deletions in males with autism spectrum disorder. American Journal of Human Genetics, 90, 879–887.PubMedCentralPubMed

38.

Charfi, C., Voisin, V., Levros, L. C., Edouard, E., & Rassert, E. (2011). Gene profiling of Graffi murine leukemia virus-induced lymphoid leukemias: identification of leukemia markers and Fmn2 as a potential oncogene. Blood, 117, 1899–1910.PubMed

39.

Akamatsu, S., Takata, R., Haiman, C. A., Takahashi, A., Inoue, T., Kubo, M., et al. (2012). Common variants at 11q12, 10q26, and 3p11.2 are associated with protease cancer susceptibility in Japanese. Nature Genetics, 44, 426–430.PubMed

40.

Hanson, D., Murray, P., Black, G., & Clayton, P. (2011). The genetics of 3-M syndrome: unravelling a potential new regulatory growth pathway. Hormone Research in Pædiatrics, 76, 369–378.PubMed

41.

McDaneld, T. G., & Spurlock, D. (2008). Ankyrin repeat and suppressor of cytokine signaling (SOCS) box-containing protein (ASB) 15 alters differentiation of mouse C2C12 myoblasts and phosphorylation of mitogen-activated protein kinase and Akt. Journal of Animal Science, 86, 2897–2902.PubMed

42.

Lahoz, A., & Hall, A. (2012). A tumor suppressor role for srGAP3 in mammary epithelial cells. Oncogene. doi:10.1038/onc.2012.489.PubMed

43.

Rimkunas, V. M., Crosby, K., Li, D., Hu, Y., Kelly, M. E., Gu, T. L., et al. (2012). Analysis of receptor tyrosine kinase ROS1- positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion. Clinical Cancer Research, 18, 4449–4457.PubMed

44.

Wu, R.-C., Wang, T.-L., & Shih, I.-M. (2014). The emerging roles of ARID1A in tumor suppression. Cancer Biology and Therapy, 15, 655–664.PubMed

45.

Witkiewicz, A. K., Knudsen, K. E., Dicker, A. P., & Knudsen, E. S. (2011). The meaning of of p16(ink4a) expression in tumors: functional significance, clinical associations, and future developments. Cell Cycle, 15, 2497–2503.

46.

Liu, W., Morito, D., Takashima, S., Mineharu, Y., Kobayashi, H., Hitomi, T., et al. (2011). Identification of RNF213 as susceptibility gene for Moyamoya disease and its possible role in vascular development. PLoS One, 6, e22542.PubMedCentralPubMed

47.

Mandai, K., Rikitake, Y., Shimono, Y., & Takai, Y. (2013). Afadin/AF-6 and canoe: roles in cell adhesion and beyond. Progress in Molecular Biology and Translational Science, 116, 433–454.PubMed

48.

Cheung, N., So, C. W., Yam, J. W. P., So, C. K. C., Poon, R. Y. C., Jin, D. Y., et al. (2004). Subcellular localization of EEN/endophilin A2, a fusion partner gene in leukaemia. Biochemistry Journal, 383, 27–35.

49.

Meissner, B., Kridel, R., Lim, R., Rogic, S., Tse, K., Scott, D. W., et al. (2013). The E3 ubiquitin ligase UBR5 is recurrently mutated in mantle cell lymphoma. Blood, 121, 3161–3164.PubMed

50.

Ye, Y., Pringle, L., Lau, A., Riquelme, D., Wang, H., Jiang, T., et al. (2010). TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NK-kappa beta. Oncogene, 29(3619–29).

51.

vanHaaften, G., Dalgliesh, G. L., Davies, H., Chen, L., Bignell, G., Greenman, C., et al. (2009). Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nature Genetics, 41, 521–523.

52.

Bjornsson, J., Short, M. P., Kwiatkowski, D. J., & Henske, E. (1996). Tuberous sclerosis-associated renal cell carcinoma. American Journal of Pathology, 149, 1201–1208.PubMedCentralPubMed

53.

Zbar, B., Glenn, G., Merino, M., Middelton, L., Peterson, J., Toro, J., et al. (2007). Familial renal carcinoma: clinical evaluation, clinical subtypes and risk of renal carcinoma development. Journal of Urology, 177, 461–465.PubMed

54.

Farley, M., Schmidt, L., Mester, J., Pena-Llopis, S., Pavia-Jimenez, A., Christie, A., et al. (2013). A novel germline BAP1 mutation predisposes to familial clear-cell renal cell carcinoma. Molecular Cancer Research, 11, 1061–1071.PubMedCentralPubMed

55.

Lonser, R. R., Glenn, G. M., Walther, M., Chew, E. Y., Libutti, S. K., Lineham, W. M., et al. (2003). von Hippel-Lindau disease. Lancet, 361, 2059–2067.PubMed

56.

Linehan, W. M., Pinto, P. A., Bratslavsky, G., Pfaffenroth, E., Merino, M., Vocke, C. D., et al. (2009). Hereditary kidney cancer: unique opportunity for disease-based therapy. Cancer, 115, 2252–2261.PubMedCentralPubMed

57.

Schmidt, L., Junker, K., Nakaigawa, N., Kinjerski, T., Weirich, G., Miller, M., et al. (1999). Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene, 18, 2343–2350.PubMed

58.

Schmidt, L., Junker, K., Weirich, G., Glenn, G., Choyke, P., Lubensky, I., et al. (1998). Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Research, 58, 1719–1722.PubMed

59.

Coleman, J. A., & Russo, P. (2009). Hereditary and familial kidney cancer. Current Opinion in Urology, 19, 478–485.PubMed

60.

Toro, J., Wei, M., Glen, G., Weinreich, M., Toure, O., Vocke, C., et al. (2008). BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports. Journal of Medical Genetics, 45, 321–331.PubMedCentralPubMed

61.

Shuin, T., Tamasaki, I., Tamura, K., Okuda, H., Furihata, M., & Ashida, S. (2006). Von Hippel-Lindau disease: molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment. Japanese Journal of Clinical Oncology, 36, 337–343.PubMed

62.

Popova, T., Hebert, L., Jacquemin, V., Gad, S., Caux-Moncoutier, V., Dubois-d’Enghien, C., et al. (2013). Germline BAP1 mutations predispose to renal cell carcinoma. American Journal of Human Genetics. doi:10.1016/j.ajhg/2013.1004.1012.PubMedCentralPubMed

63.

Macher-Goeppinger, S., Roth, W., Wagener, N., Hohenfellner, M., Penzel, R., Haferkamp, A., et al. (2012). Molecular heterogeneity of TFE activation in renal cell carcinoma. Modern Pathology, 25, 308–315.PubMed

64.

Klaassen, Z., Tatem, A., Burnette, J. O., Donohoe, J. M., & Terris, M. K. (2012). Adult Xp11 translocation associated renal cell carcinoma: time to recognize. Urology, 80, 965–968.PubMed

65.

Audenet, F., Yates, D. R., Cancel-Tassin, G., Cussenot, O., & Roupret, M. (2011). Genetic pathways involved in carcinogenesis of clear cell renal cell carcinoma: genomics towards personalized medicine. BJU International, 12, 1864–1870.

66.

Shen, C., & Kaelin, W. G. (2013). The VHL/HIF axis in clear cell renal carcinoma. Seminars in Cancer Biology, 23, 18–25.PubMedCentralPubMed

67.

Choueiri, T. K., Pomerantz, M. M., & Signoretti, S. (2013). Renal-cell carcinoma: a step closer to a new classification. Lancet Oncology, 14, 105–106.

68.

Pollack, J. R., & Shain, A. H. (2013). The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS One, 8(1), e55119. doi:10.1371/journal.pone.0055119.PubMedCentralPubMed

69.

Kapur, P., Pena-Llopis, S., Christie, A., Zhrebker, L., Pavia-Jimenez, A., Rathmell, W. K., et al. (2013). Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncology, 14, 159–167.

70.

Morales, C., Kurban, G., Yap, S., Matevski, D., Evans, A., & Jewett, M. A. (2012). Clinical role of the SWI/SNF complex gene PBRM1 in clear cell renal cell carcinoma [abstract] (pp. 31–32). Rockville: 13th Annual Meeting of the Society of Urologic Oncology.

71.

Pawlowski, R., Muhl, S. M., Sulser, T., Krek, W., Moch, H., & Schraml, P. (2013). Loss of PBRM1 expression is associated with renal cell carcinoma progression. International Journal of Cancer, 132, E11–E17.

72.

Carbone, M., Yang, H., Pass, H., Krausz, T., Testa, J. R., & Gaudino, G. (2013). BAP1 and cancer. Nature Reviews Cancer, 13, 153–159.PubMedCentralPubMed

73.

Jensen, D. E., Proctor, M., Marquis, S. T., Gardner, H. P., Ha, S. I., Chodosh, L. A., et al. (1998). BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene, 16, 1097–1112.PubMed

74.

Bott, M., Brevet, M., Taylor, B. S., Shimizu, S., Ito, T., Wang, L., et al. (2011). The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nature Genetics, 43, 668–672.PubMed

75.

Cancer Genome Atlas Network. (2013). Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499, 43–49.

76.

DeVita, V. T., Lawrence, T. S., & Rosenberg, S. A. (2008). Cancer: principles and practice of oncology (8th ed.). New York: Wolters Kluwer/Lippincott Williams & Wilkins.

77.

Vanharata, S., Shu, W., Brenet, F., Hakimi, A. A., Heguy, A., Viale, A., et al. (2012). Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Nature Medicine, 19, 53–56.

78.

Staller, P., Sulitkova, J., Lisztwan, J., Moch, H., Oakeley, E., & Krek, W. (2003). Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature, 425, 307–311.PubMed

79.

Zagzag, D., Krishnamachary, B., Yee, H., Okuyama, H., Chiriboga, L., Ali, M. A., et al. (2005). Stromal cell-derived factor-1a and CXCR4 expression in hemangioblastoma and clear cell-renal cell carcinoma: von Hippel-Lindau loss-of-function induces expression of a ligand and its receptor. Cancer Research, 65, 6178–6188.PubMed

80.

Wang, L., Chen, W., Gao, L., Yang, Q., Liu, B., Wu, Z., et al. (2012). High expression of CXCR4, CXCR7, and SDF-1 predicts poor survival in renal cell carcinoma. World Journal of Surgical Oncology, 10, 212.PubMedCentralPubMed

81.

Wang, L., Wang, L., Yang, B., Yang, Q., Qiao, S., Wang, Y., et al. (2009). Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis. Clinical and Experimental Metastasis, 26, 1049–1054.PubMed

82.

Gassenmaier, M., Chen, D., Buchner, A., Henkel, L., Schiemann, M., Mack, B., et al. (2013). CXC chemokine receptor 4 is essential for maintenance of renal cell carcinoma-initiating cells and predicts metastasis. Stem Cells, 31, 1467–1476.PubMed

83.

Klapper, J. A., Downey, S. G., Smith, F., Yang, J. C., Hughes, M. S., Kammula, U. S., et al. (2008). High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer, 113, 293–301.PubMedCentralPubMed

84.

Rini, B., de La Motte Rouge, T., Harzstark, A., Michaelson, M. D., Liu, G., Grunwald, V., et al. (2013). Five-year survival in patients with cytokine-refractory metastatic renal cell carcinoma treated with axitinib. Clinical Genitourinary Cancer, 11, 107–114.PubMed

85.

DiBiase, S., Valicenti, R., Schultz, D., Xie, Y., Gomella, L., & Corn, B. (1997). Palliative irradiation for focally symptomatic metastatic renal cell carcinoma: support for dose escalation based on a biological model. Journal of Urology, 158, 746–749.PubMed

86.

Karam, J., & Wood, C. (2011). The role of surgery in advance renal cell carcinoma: cytoreductive nephrectomy and metastectomy. Hematology/oncology Clinics of North America, 25, 753–764.PubMed

87.

Silberstein, J., Millard, F., Mehrazin, R., Kopp, R., Bazzi, W., DiBlasio, C., et al. (2010). Feasiblity and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. BJU International, 106, 1270–1276.PubMed

88.

Kapoor, A., Wang, Y., Dishan, B., & Paulter, S. (2014). Update on cryoablation for treatment of small renal mass: oncologic control, renal function preservation, and rate of complications. Current Urology Reports, 15, 396.PubMed

89.

Li, D., Pua, B., & Madoff, D. (2014). Role of embolization in the treatment of renal masses. Seminars in Interventional Radiology, 31, 70–81.PubMed

90.

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

91.

Heng, D. Y., Rini, B., Beuselinck, B., Lee, J., Knox, J. J., Bjarnason, G. A., et al. (2014). Cytoreductive nephrectomy (CN) in patients with synchronous metastases from renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium (IMDC). Journal of Clinical Oncology, 32(suppl 4), 396.

92.

Rini, B. I., Escudier, B., Tomczak, 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. Lancet, 378, 1931–1939.PubMed

93.

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 randomised, double-blind phase III trial. Lancet, 370, 2103–2111.PubMed

94.

Houghton, P. J. (2010). Everolimus. Clinical Cancer Research, 16, 1368–1372.PubMedCentralPubMed

95.

Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., et al. (2010). Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and prognostic factors. Cancer, 116(18), 4256–4265.PubMed

96.

Coppin, C., Porzolt, F., Autenrieth, M., Kumpf, J., Coldman, A., & Wilt, T. (2004). Immunotherapy for advanced renal cell cancer. Cochrane Database of Systematic Reviews, 3, CD001425.

97.

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. Journal of Clinical Oncology, 28, 1061–1068.PubMed

98.

Sternberg, C. N., Hawkins, R. E., Wagstaff, J., Salman, P., Mardiak, J., Barrios, C. H., et al. (2013). A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. European Journal of Cancer, 49, 1287–1296.PubMed

99.

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

100.

Chow, L. Q. M., & Eckhart, S. G. (2007). Sunitinib: from rational design to clinical efficacy. Journal of Clinical Oncology, 25, 884–896.PubMed

101.

Motzer, R. J., Hutson, T. E., Tomczak, P., Michaelson, M. D., Bukowski, R. M., Oudard, S., et al. (2009). Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 27, 3584–3590.PubMedCentralPubMed

102.

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. New England Journal of Medicine, 356, 2271–2281.PubMed

103.

Lockhart, A. C., Rothenberg, M. L., Dupont, J., Cooper, W., Chevalier, P., Sternas, L., et al. (2010). Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. Journal of Clinical Oncology, 28, 207–214.PubMedCentralPubMed

104.

Amin, A., Dudek, A., Logan, T., Lance, R. S., Holzbeierlein, J. M., Master, V. A., et al. (2013). Prolonged survival with personalized immunotherapy (AGS-003) in combination with sunitinib in unfavorable risk metastatic RCC (mRCC). Journal of Clinical Oncology, 31(suppl), 357.

105.

Sarantopoulos, J., Dang, L. H., Lauer, R., Starodub, A., Hauke, R. J., Galsky, M. D., et al. (2013). A phase I/II trial of BNC105P with everolimus in metastatic renal cell carcinoma (mRCC) patients: updated phase I results of the disruptor-1 trial. Journal of Clinical Oncology, 31(suppl), 4563.

106.

Mekhail, T., Masson, E., Fischer, B. S., Gong, J., Iyer, R., Gan, J., et al. (2010). Metabolism, excretion, and pharmacokinetics of oral brivanib in patients with advanced or metastatic solid tumors. Drug Metabolism and Disposition, 38, 1962–1966.PubMedCentralPubMed

107.

Finn, R. S., Kang, Y. K., Muchahy, M., Polite, B. N., Lim, H. Y., Walters, I., et al. (2012). Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma. Clinical Cancer Research, 18, 2090–2098.PubMed

108.

Choueiri, T. K., Pal, S. K., McDermott, D. F., Ramies, D. A., Morrisey, S., Lee, Y., et al. (2012). Efficacy of cabozantinib (XL184) in patients (pts) with metastatic, refractory renal cell carcinoma (RCC). Journal of Clinical Oncology, 30(suppl), 4504.

109.

Sridhar, S. S., Mackenzie, M. J., Hotte, S. J., Mukherjee, S. D., Tannock, I. F., Murray, N., et al. (2013). A phase II study of cediranib (AZD 2171) in treatment naive patients with progressive unresectable recurrent or metastatic renal cell carcinoma. A trial of the PMH phase 2 consortium. Investigational New Drugs. doi:10.1007/s10637-013-9931-1.PubMed

110.

Keefe, S. M., Heitjan, D., Hennessey, M., Robinson, J., Mykulowicz, K., Marshall, A., et al. (2014). Interim results of a phase 1b/2a study evaluating the nano pharmaceutical CRLX101 with bevacizumab (bev) in the treatment of patients (pts) with refractory metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology, 32(suppl), 412.

111.

Bendell, J., Gordon, M. S., Hurwitz, H., Condon, C., Yang, Y., Wilson, D., et al. (2011). Phase I study of ACE-041, a novel inhibitor of ALK1-mediated angiogenesis, in patients with advanced solid tumors. Journal of Clinical Oncology, 29(suppl), 3070.

112.

Angevin, E., Lopez-Martin, J. A., Lin, C. C., Gschwend, J. E., Harzstark, A., Castellano, D., et al. (2012). Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. Clinical Cancer Research, 19(5), 1257–1268.

113.

Angevin, E., Grunwald, V., Ravaud, A., Castellano, D. E., Lin, C. C., Gschwend, J. E., et al. (2011). A phase II study of dovitinib (TKI258), an FGFR and VEGFR inhibitor, in patients with advanced or metastatic renal cell cancer (mRCC). Journal of Clinical Oncology, 29(suppl), 4551.

114.

Motzer, R. J., Porta, C., Vogelzang, N. J., Sternberg, C. N., Szczylik, C., Zolnierek, J., et al. (2014). Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open label, randomised phase 3 trial. Lancet Oncology, 15, 286–296.

115.

Pili, R., Shen, L., George, S., Hammers, H. J., Sandecki, A., Collins, C., et al. (2013). Phase I study of high-dose interleukin 2, aldesleukin, in combination with the histone deacetylase inhibitor, entinostat, in patients with metastatic renal cell carcinoma: safetly and tolerability results. Journal of Clinical Oncology, 31(suppl), 369.

116.

Choueiri, T. K., Vaishampayan, U., Rosenberg, J. E., Logan, T. F., Harzstark, A., Bukowski, R. M., et al. (2013). Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. Journal of Clinical Oncology, 31, 181–186.PubMedCentralPubMed

117.

Belldegrun, A. S., Chamie, K., Kloepfer, P., Fall, B., Bevan, P., Storkel, S., et al. (2013). ARISER: a randomised double blind phase III study to evaluate adjuvant cG250 treatment versus placebo in patients with high-risk ccRCC—results and implications for adjuvant clinical trials. Journal of Clinical Oncology, 31(suppl), 4507.

118.

Walter, S., Weinschenk, T., Stenzl, A., Zdrojowy, R., Pluzanska, A., Szczylik, C., et al. (2012). Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nature Medicine, 18, 1254–1261.PubMed

119.

Bang, Y.-J., Su, W. C., Nam, D. H., Lim, W. T., Bauer, T. M., Brana, I., et al. (2014). Phase I study of the safety and efficacy of INC280 in patients with advanced MET-dependent solid tumors. Journal of Clinical Oncology, 32(suppl), 2520.

120.

Molina, A. M., Hutson, T. E., Larkin, J. M., Gold, A., Andresen, C., Wood, K., et al. (2013). A phase Ib clinical trial of the multitargeted kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC). Journal of Clinical Oncology, 31(suppl 6), 358.

121.

Tannir, N. M., Wong, Y. N., Kollmannsberger, C. K., Ernstoff, M. S., Perry, D. J., Appleman, L. J., et al. (2011). Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure. European Journal of Cancer, 47, 2706–2714.PubMedCentralPubMed

122.

Ghamande, S., Lin, C., Cho, D., Coleman, T., Chaudhary, I., Cleary, J., et al. (2011). A phase I study of the novel DNA topoisomerase-1 inhibitor, TLC388, administered intravenously to patients with advanced solid tumors. Journal of Clinical Oncology, 29(suppl), e13618.

123.

Jonasch, E., Corn, P. G., Pagliaro, L. C., Lara, P., Wang, X., Do, K.-A., et al. (2013). Randomized phase II CTEP study of MK2206 versus everolimus in VEGF inhibitor refractory renal cell carcinoma patients. Journal of Clinical Oncology, 31(suppl), 4517.

124.

Cho, D. C., Sosman, J. A., Sznol, M., Gordon, M. S., Hollebecque, A., Hamid, O., et al. (2013). Clinical activity, safety, and biomarkers of MPDL3230A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology, 31(suppl), 4505.

125.

Borghaei, H., Alpaugh, K., Hedlund, G., Forsberg, G., Langer, C., Rogatko, A., et al. (2009). Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer. Journal of Clinical Oncology, 27, 4116–4123.PubMedCentralPubMed

126.

Hawkins, R. E., Gore, M. E., Shparyk, Y., Bondar, V., Gladkov, O., Ganev, T., et al. (2013). A randomized phase II/III study of naptumomab estafenatox plus IFN-a versus IFN-a in advanced renal cell carcinoma. Journal of Clinical Oncology, 31(suppl), 3073.

127.

Eisen, T., Shparyk, Y., Jones, R., MacLeod, N. J., Temple, G., Finnigan, H., et al. (2013). Phase II efficacy and safety study of nintedanib versus sunitinib in previously untreated renal cell carcinoma (RCC) patients. Journal of Clinical Oncology, 31(suppl), 4506.

128.

Topalian, S. L., Hodi, S. F., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New England Journal of Medicine, 366, 2443–2454.PubMedCentralPubMed

129.

Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., et al. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New England Journal of Medicine, 366, 2455–2465.PubMedCentralPubMed

130.

Ribas, A., Hodi, S. F., Kefford, R., Hamid, O., Daud, A., Wolchok, J. D., et al. (2014). Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients with melanoma (MEL). Journal of Clinical Oncology, 32(suppl), LBA9000.

131.

Atkins, M. B., Kudchadkar, R. R., Sznol, M., McDermott, D. F., Lotern, M., Schachter, J., et al. (2014). Phase 2, multicenter, safety and efficacy of pidilizumab in patients with metastatic melanoma. Journal of Clinical Oncology, 32(suppl), 9001.

132.

Garcia, J. A., Hudes, G. R., Choueiri, T. K., Stadler, W. M., Wood, L. S., Gurtler, J., et al. (2014). A phase 2, single-arm study of ramucirumab in patients with metastatic renal cell carcinoma with disease progression on or intolerance to tyrosine kinase inhibitor therapy. Cancer, 120, 1647–1655.PubMed

133.

Eisen, T., Joensuu, H., Nathan, P. D., Harper, P. G., Wojtukiewicz, M. Z., Nicholson, S., et al. (2012). Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncology, 13, 1055–1062.

134.

Schoffski, P., Garcia, J. A., Stadler, W. M., Gil, T., Jonasch, E., Tagawa, S. T., et al. (2011). A phase II study of the efficacy and safety of AMG 102 in patients with metastatic renal cell carcinoma. BJU International, 108, 679–686.PubMed

135.

Gordon, M., Just, R., Rosen, L., & Dorr, A. (2010). A phase I study of sonepiczumab (S), a humanized monoclonal antibody to sphingosine-1-phosphate (S1P), in patients with advanced solid tumors. Journal of Clinical Oncology, 28(suppl), 2560.

136.

Puzanov, I., Sosman, J. A., Santoro, A., Martell, R. E., Dy, G. K., Goff, L. W., et al. (2012). Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with renal cell carcinoma (RCC) from a phase I study. Journal of Clinical Oncology, 30(suppl), 4545.

137.

Rosen, L. S., Senzer, N., Mekhail, T., Ganapathi, R., Chai, F., Savage, R. E., et al. (2011). A phase I dose-escalation study of tivantinib (ARQ 197) in adult patients with metastatic solid tumors. Clinical Cancer Research, 17, 7754–7764.PubMed

138.

Motzer, R. J., Nosov, D., Eisen, T., Bondarenko, I. N., Lesovoy, V., Lipatov, O. N., et al. (2012). Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: results from a phase III randomized, open-label, multicenter trial. Journal of Clinical Oncology, 30(suppl), 4501.

139.

Motzer, R. J., Nosov, D., Eisen, T., Bondarenko, I., Lesovoy, V., Lipatov, O. N., et al. (2013). Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. Journal of Clinical Oncology, 31, 3791–3799.PubMed

140.

Rini, B. I., Szczylik, C., Tannir, N. M., Koralewski, P., Tomczak, P., Deptala, A., et al. (2011). AMG 386 in combination with sorafenib in patients (pts) with metastatic renal cell cancer (mRCC): a randomized, double-blind, placebo-controlled, phase II study. Journal of Clinical Oncology, 29(suppl), 309.

141.

Stamatakis, L., Shuch, B., Singer, E. A., Nix, J., Truong, H., Friend, J. C., et al. (2013). Phase II trial of vandetanib in Von Hippel-Lindau-associated renal cell carcinoma. Journal of Clinical Oncology, 31(suppl), 4584.

142.

Gan, H. K., Lickliter, J., Millward, M., Gu, Y., Su, W., Frigault, M., et al. (2014). First-in-human phase I study of a selective c-Met inhibitor volitinib (HMP504/AZD6094) in patients with advanced solid tumors. Journal of Clinical Oncology, 32(suppl), 11111.

143.

van Geel, R. M., Beijnen, J., & Schellens, J. (2012). Concise drug review, pazopanib and axitinib. The Oncologist, 17, 1081–1089.PubMedCentralPubMed

144.

Motzer, R. J., Hutson, T. E., Cella, D., Reeves, J., Hawkins, R., Guo, J., et al. (2013). Pazopanib versus sunitinib in metastatic renal-cell carcinoma. New England Journal of Medicine, 369, 722–731.PubMed

145.

McDermott, D., Ghebremichael, S., Signoretti, S., Margolin, K., Clark, J., Sosman, J. A., et al. (2010). The high-dose aldesleukin (HD IL-2) select trial in patients with metastatic renal cell carcinoma (mRCC): preliminary assessment of clinical benefit. Journal of Clinical Oncology, 28(suppl), 4514.

146.

Watanabe, S., Tanaka, J., Ota, T., Kondo, R., Tanaka, H., Kagamu, H., et al. (2011). Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. BMC Cancer, 11, 1.PubMedCentralPubMed

147.

Naing, A., & Kurzrock, R. (2010). Chemotherapy resistance and retreatment: a dogma revisited. Clinical Colorectal Cancer, 9, E1–E4. doi:10.3816/CCC.2010.n.3026.PubMed

148.

Naing, A., & Kurzrock, R. (2012). Dodging a dogma: is treating beyond progression beneficial. Cancer Chemotheraphy and Pharmacology, 71, 1385–1386.

149.

Zama, I. N., Hutson, T. E., Elson, P., Cleary, J. M., Choueiri, T. K., Heng, D. Y., et al. (2010). Sunitinib rechallenge in metastatic renal cell carcinoma patients. Cancer, 116, 5400–5406.PubMed

150.

Rini, B., Bellmunt, J., Clancy, J., Wang, K., Niellhammer, A., & Escudier, B. (2013). Randomized phase IIIB trial of temsirolimus and bevacizumab versus interferon and bevacizumab in metastatic renal cell carcinoma: results from intoract. Annals of Oncology, 23(suppl), LBA21_PR.

151.

McDermott, D. F., Manola, J., Pins, M., Flaherty, K. T., Atkins, M. B., Dutcher, J., et al. (2013). The best trial (E2804): a randomized phase II study of VEGF, RAF kinase, and mTOR combination targeted therapy (CTT) with bevacizumab (bev), sorafenib (sor), and temsirolimus (tem) in advanced renal cell carcinoma (RCC). Journal of Clinical Oncology, 31(suppl), 345.

152.

Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A., et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. New England Journal of Medicine, 369, 122–133.PubMed

153.

Henary, H., Hong, D. S., Falchook, G. S., Tsimberidou, A., George, G., Wen, S., et al. (2013). Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes. Annals of Oncology, 24, 2158–2165.PubMedCentralPubMed

154.

Tsimberidou, A.-M., Iskander, N., Hong, D. S., Wheeler, J. J., Falchook, G., Fu, S., et al. (2012). Personalized medicine in a phase I clinical trials program: the MD Anderson cancer center initiative. Clinical Cancer Research, 18, 6373–6383.PubMed

155.

Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., et al. (2011). Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine, 364, 2507–2516.PubMedCentralPubMed

156.

Kwak, E., Bang, Y.-J., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., et al. (2010). Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New England Journal of Medicine, 363, 1693–1703.PubMedCentralPubMed

157.

Janku, F., Berry, D. A., Gong, J., Parsons, H. A., Stewart, D. J., & Kurzrock, R. (2012). Outcomes of phase II clinical trials with single-agent therapies in advanced/metastatic non-small cell lung cancer published between 2000 and 2009. Clinical Cancer Research, 18, 6356–6363.PubMed

158.

Janku, F., Wheler, J., Westin, S. N., Moulder, S. L., Naing, A., Tsimberidou, A. M., et al. (2012). PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. Journal of Clinical Oncology, 30, 777–782.PubMedCentralPubMed

159.

Voss, M. H., Hakimi, A. A., Scott, S. N., Takeda, S., Liu, H., Chen, Y., et al. (2012). Genetic determinants of long-term response to rapalog therapy in advanced renal cell carcinoma (RCC). Journal of Clinical Oncology, 30(suppl), 4604.

160.

Said, R., Hong, D. S., Warenke, C. L., Lee, J. J., Wheeler, J. J., Janku, F., et al. (2013). P53 mutations in advanced cancers: clinical characteristics, outcomes, and correlation between progression-free survival and bevacizumab-containing therapy. Oncotarget, 4, 705–714.PubMedCentralPubMed

161.

Chung, A., Wu, X., Zhuang, G., Ngu, H., Kasman, I., Zhang, J., et al. (2013). An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy. Nature Medicine, 19, 1114–1123.PubMed

162.

Westin, J. R., & Kurzrock, R. (2012). It's about time: lessons for solid tumors from chronic myelogenous leukemia therapy. Molecular Cancer Therapeutics, 11, 2549–2555.

163.

Smaldone, M. C., Fung, C., Uzzo, R., & Haas, N. B. (2011). Adjuvant and neoadjuvant therapies in high-risk renal cell carcinoma. Hematology/oncology Clinics of North America, 25, 765–791.PubMed

Titel: Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art
verfasst von: J. Michael Randall
Frederick Millard
Razelle Kurzrock
Publikationsdatum: 01.12.2014
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 4/2014
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-014-9533-1

Springer Medizin

Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2014

Emerging roles of regulatory T cells in tumour progression and metastasis

Post-transcriptional regulation of MTA family by microRNAs in the context of cancer

MTA family of proteins in DNA damage response: mechanistic insights and potential applications

Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

Role of MTA1 in head and neck cancers

Metastatic tumor antigen in hepatocellular carcinoma: golden roads toward personalized medicine

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie