Top

Published in:

Open Access 01-12-2009

Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer

Authors: Margaret A. Knowles, Fiona M. Platt, Rebecca L. Ross, Carolyn D. Hurst

Published in: Cancer and Metastasis Reviews | Issue 3-4/2009

Abstract

The phosphatidylinositol 3-kinase (PI3K) pathway is a critical signal transduction pathway that regulates multiple cellular functions. Aberrant activation of this pathway has been identified in a wide range of cancers. Several pathway components including AKT, PI3K and mTOR represent potential therapeutic targets and many small molecule inhibitors are in development or early clinical trials. The complex regulation of the pathway, together with the multiple mechanisms by which it can be activated, make this a highly challenging pathway to target. For successful inhibition, detailed molecular information on individual tumours will be required and it is already clear that different tumour types show distinct combinations of alterations. Recent results have identified alterations in pathway components PIK3CA, PTEN, AKT1 and TSC1 in bladder cancer, some of which are significantly related to tumour phenotype and clinical behaviour. Co-existence of alterations to several PI3K pathway genes in some bladder tumours indicates that these proteins may have functions that are not related solely to the known canonical pathway.

Cantley, L. C. (2002). The phosphoinositide 3-kinase pathway. Science, 296, 1655–1657.CrossRefPubMed

Luo, J., Manning, B. D., & Cantley, L. C. (2003). Targeting the PI3K-Akt pathway in human cancer: rationale and premise. Cancer Cell, 4, 257–262.CrossRefPubMed

Shaw, R. J., & Cantley, L. C. (2006). Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature, 441, 424–430.CrossRefPubMed

Eng, C. (2003). PTEN: one gene, many syndromes. Human Mutation, 22, 183–198.CrossRefPubMed

Launonen, V. (2005). Mutations in the human LKB1/STK11 gene. Human Mutation, 26, 291–297.CrossRefPubMed

Philp, A. J., Campbell, I. G., Leet, C., Vincan, E., Rockman, S. P., Whitehead, R. H., et al. (2001). The phosphatidylinositol 3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Research, 61, 7426–7429.PubMed

Parsons, D. W., Wang, T. L., Samuels, Y., Bardelli, A., Cummins, J. M., DeLong, L., et al. (2005). Colorectal cancer: mutations in a signalling pathway. Nature, 436, 792.CrossRefPubMed

Samuels, Y., & Ericson, K. (2006). Oncogenic PI3K and its role in cancer. Current Opinion in Oncology, 18, 77–82.CrossRefPubMed

Carpten, J. D., Faber, A. L., Horn, C., Donoho, G. P., Briggs, S. L., Robbins, C. M., et al. (2007). A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature, 448, 439–444.CrossRefPubMed

10.

Ramjaun, A. R., & Downward, J. (2007). Ras and phosphoinositide 3-Kinase: partners in development and tumorigenesis. Cell Cycle, 66(23), 2902–2905.

11.

Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005). Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell, 121, 179–193.CrossRefPubMed

12.

Yuan, T. L., & Cantley, L. C. (2008). PI3K pathway alterations in cancer: variations on a theme. Oncogene, 27, 5497–5510.CrossRefPubMed

13.

Wu, X. R. (2005). Urothelial tumorigenesis: a tale of divergent pathways. Nature Reviews Cancer, 5, 713–725.CrossRefPubMed

14.

Knowles, M. A. (2006). Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis, 27, 361–373.CrossRefPubMed

15.

Knowles, M. A. (2008). Bladder cancer subtypes defined by genomic alterations. Scandinavian Journal of Urology and Nephrology 42(S218t) 116-130.

16.

Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005). Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307, 1098–1101.CrossRefPubMed

17.

Bozulic, L., Surucu, B., Hynx, D., & Hemmings, B. A. (2008). PKBalpha/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival. Molecular Cell, 30, 203–213.CrossRefPubMed

18.

Cappellen, D., Diez, G., de Medina, S., Chopin, D., Thiery, J. P., & Radvanyi, F. (1997). Frequent loss of heterozygosity on chromosome 10q in muscle-invasive transitional cell carcinomas of the bladder. Oncogene, 14, 3059–3066.CrossRefPubMed

19.

Cairns, P., Evron, E., Okami, K., Halachmi, N., Esteller, M., Herman, J. G., et al. (1998). Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene, 16, 3215–3218.CrossRefPubMed

20.

Aveyard, J. S., Skilleter, A., Habuchi, T., & Knowles, M. A. (1999). Somatic mutation of PTEN in bladder carcinoma. British Journal of Cancer, 80, 904–908.CrossRefPubMed

21.

Wang, D. S., Rieger-Christ, K., Latini, J. M., Moinzadeh, A., Stoffel, J., Pezza, J. A., et al. (2000). Molecular analysis of PTEN and MXI1 in primary bladder carcinoma. International Journal of Cancer, 88, 620–625.CrossRef

22.

Zhao, L., & Vogt, P. K. (2008). Helical domain and kinase domain mutations in p110(alpha) of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 105, 2652–2657.CrossRefPubMed

23.

Platt, F. M., Hurst, C. D., Taylor, C. F., Gregory, W. M., Harnden, P., & Knowles, M. A. (2009). Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer. Clinical Cancer Research, 15, 6008–6017.CrossRefPubMed

24.

Lopez-Knowles, E., Hernandez, S., Malats, N., Kogevinas, M., Lloreta, J., Carrato, A., et al. (2006). PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Research, 66, 7401–7404.CrossRefPubMed

25.

Hurst, C. D., Zuiverloon, T. C., Hafner, C., Zwarthoff, E. C., & Knowles, M. A. (2009). A SNaPshot assay for the rapid and simple detection of four common hotspot codon mutations in the PIK3CA gene. BMC Research Notes, 2, 66.CrossRefPubMed

26.

Samuels, Y., & Velculescu, V. E. (2004). Oncogenic mutations of PIK3CA in human cancers. Cell Cycle, 3, 1221–1224.PubMed

27.

Jebar, A. H., Hurst, C. D., Tomlinson, D. C., Johnston, C., Taylor, C. F., & Knowles, M. A. (2005). FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene, 24, 5218–5225.CrossRefPubMed

28.

Billerey, C., Chopin, D., Aubriot-Lorton, M. H., Ricol, D., Diez, G., de Medina, S., et al. (2001). Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. American Journal of Pathology, 158, 1955–1959.PubMed

29.

Hafner, C., Lopez-Knowles, E., Luis, N. M., Toll, A., Baselga, E., Fernandez-Casado, A., et al. (2007). Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proceedings of the National Academy of Sciences of the United States of America, 104, 13450–13454.CrossRefPubMed

30.

Gu, J., Tamura, M., Pankov, R., Danen, E. H., Takino, T., Matsumoto, K., et al. (1999). Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. Journal of Cell Biology, 146, 389–403.CrossRefPubMed

31.

Planchon, S. M., Waite, K. A., & Eng, C. (2008). The nuclear affairs of PTEN. Journal of Cell Science, 121, 249–253.CrossRefPubMed

32.

Kagan, J., Liu, J., Stein, J. D., Wagner, S. S., Babkowski, R., Grossman, B. H., et al. (1998). Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer. Oncogene, 16, 909–913.CrossRefPubMed

33.

Liu, J., Babaian, D. C., Liebert, M., Steck, P. A., & Kagan, J. (2000). Inactivation of MMAC1 in bladder transitional-cell carcinoma cell lines and specimens. Molecular Carcinogenesis, 29, 143–150.CrossRefPubMed

34.

Tsuruta, H., Kishimoto, H., Sasaki, T., Horie, Y., Natsui, M., Shibata, Y., et al. (2006). Hyperplasia and carcinomas in pten-deficient mice and reduced PTEN Protein in human bladder cancer patients. Cancer Research, 66, 8389–8396.CrossRefPubMed

35.

Puzio-Kuter, A. M., Castillo-Martin, M., Kinkade, C. W., Wang, X., Shen, T. H., Matos, T., et al. (2009). Inactivation of p53 and Pten promotes invasive bladder cancer. Genes and Development, 23, 675–680.CrossRefPubMed

36.

Di Cristofano, A., Pesce, B., Cordon-Cardo, C., & Pandolfi, P. P. (1998). Pten is essential for embryonic development and tumour suppression. Nature Genetics, 19, 348–355.CrossRefPubMed

37.

Wu, X., Obata, T., Khan, Q., Highshaw, R. A., De Vere White, R., & Sweeney, C. (2004). The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion. BJU International, 93, 143–150.CrossRefPubMed

38.

Dey, N., Crosswell, H. E., De, P., Parsons, R., Peng, Q., Su, J. D., et al. (2008). The protein phosphatase activity of PTEN regulates SRC family kinases and controls glioma migration. Cancer Research, 68, 1862–1871.CrossRefPubMed

39.

Chiang, G. J., Billmeyer, B. R., Canes, D., Stoffel, J., Moinzadeh, A., Austin, C. A., et al. (2005). The src-family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt. BJU International, 96, 416–422.CrossRefPubMed

40.

Gildea, J. J., Herlevsen, M., Harding, M. A., Gulding, K. M., Moskaluk, C. A., Frierson, H. F., et al. (2004). PTEN can inhibit in vitro organotypic and in vivo orthotopic invasion of human bladder cancer cells even in the absence of its lipid phosphatase activity. Oncogene, 23, 6788–6797.CrossRefPubMed

41.

Yoo, L. I., Liu, D. W., Le Vu, S., Bronson, R. T., Wu, H., & Yuan, J. (2006). Pten deficiency activates distinct downstream signaling pathways in a tissue-specific manner. Cancer Research, 66, 1929–1939.CrossRefPubMed

42.

Askham, J. M., Platt, F., Chambers, P. A., Snowden, H., Taylor, C. F., & Knowles, M. A. (2009). AKT1 mutations in bladder cancer: identification of a novel oncogenic mutation that can co-operate with E17K. Oncogene (in press)

43.

Gomez, M., Sampson, J., & Whittemore, V. (1999). The tuberous sclerosis complex. Oxford University Press.

44.

van Slegtenhorst, M., de Hoogt, R., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., et al. (1997). Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 277, 805–808.CrossRefPubMed

45.

Consortium. (1993). Identification and characterization of the tuberous sclerosis gene on chromosome 16. The European chromosome 16 tuberous sclerosis consortium. Cell, 75, 1305–1315.

46.

Plank, T. L., Yeung, R. S., & Henske, E. P. (1998). Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Research, 58, 4766–4770.PubMed

47.

Johnson, M. W., Emelin, J. K., Park, S. H., & Vinters, H. V. (1999). Co-localization of TSC1 and TSC2 gene products in tubers of patients with tuberous sclerosis. Brain Pathology, 9, 45–54.PubMedCrossRef

48.

Hodges, A. K., Li, S., Maynard, J., Parry, L., Braverman, R., Cheadle, J. P., et al. (2001). Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Human Molecular Genetics, 10, 2899–2905.CrossRefPubMed

49.

Inoki, K., Li, Y., Xu, T., & Guan, K. L. (2003). Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes and Development, 17, 1829–1834.CrossRefPubMed

50.

Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003). Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Current Biology, 13, 1259–1268.CrossRefPubMed

51.

Hornigold, N., Devlin, J., Davies, A. M., Aveyard, J. S., Habuchi, T., & Knowles, M. A. (1999). Mutation of the 9q34 gene TSC1 in sporadic bladder cancer. Oncogene, 18, 2657–2661.CrossRefPubMed

52.

Adachi, H., Igawa, M., Shiina, H., Urakami, S., Shigeno, K., & Hino, O. (2003). Human bladder tumors with 2-hit mutations of tumor suppressor gene TSC1 and decreased expression of p27. Journal of Urology, 170, 601–604.CrossRefPubMed

53.

Cairns, P., Shaw, M. E., & Knowles, M. A. (1993). Initiation of bladder cancer may involve deletion of a tumour-suppressor gene on chromosome 9. Oncogene, 8, 1083–1085.PubMed

54.

Habuchi, T., Devlin, J., Elder, P. A., & Knowles, M. A. (1995). Detailed deletion mapping of chromosome 9q in bladder cancer: evidence for two tumour suppressor loci. Oncogene, 11, 1671–1674.PubMed

55.

Simoneau, M., Aboulkassim, T. O., LaRue, H., Rousseau, F., & Fradet, Y. (1999). Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31. Oncogene, 18, 157–163.CrossRefPubMed

56.

van Tilborg, A. A., Groenfeld, L. E., van der Kwast, T. H., & Zwarthoff, E. C. (1999). Evidence for two candidate tumour suppressor loci on chromosome 9q in transitional cell carcinoma (TCC) of the bladder but no homozygous deletions in bladder tumour cell lines. British Journal of Cancer, 80, 489–494.CrossRefPubMed

57.

Knowles, M. A., Habuchi, T., Kennedy, W., & Cuthbert-Heavens, D. (2003). Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder. Cancer Research, 63, 7652–7656.PubMed

58.

Pymar, L. S., Platt, F. M., Askham, J. M., Morrison, E. E., & Knowles, M. A. (2008). Bladder tumour derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms. Human Molecular Genetics, 17, 2006–2017.CrossRefPubMed

59.

Mozaffari, M., Hoogeveen-Westerveld, M., Kwiatkowski, D., Sampson, J., Ekong, R., Povey, S., et al. (2009). Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex. BMC Medical Genetic, 10, 88.CrossRef

60.

Nellist, M., van den Heuvel, D., Schluep, D., Exalto, C., Goedbloed, M., Maat-Kievit, A., et al. (2009). Missense mutations to the TSC1 gene cause tuberous sclerosis complex. European Journal of Human Genetics, 17, 319–328.CrossRefPubMed

61.

Henske, E. P., Scheithauer, B. W., Short, M. P., Wollmann, R., Nahmias, J., Hornigold, N., et al. (1996). Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. American Journal of Human Genetics, 59, 400–406.PubMed

62.

Cheadle, J. P., Reeve, M. P., Sampson, J. R., & Kwiatkowski, D. J. (2000). Molecular genetic advances in tuberous sclerosis. Human Genetics, 107, 97–114.CrossRefPubMed

63.

Soltoff, S. P., Carraway, K. L., 3 rd, Prigent, S. A., Gullick, W. G., & Cantley, L. C. (1994). ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Molecular and Cellular Biology, 14, 3550–3558.

64.

Moriyama, M., Akiyama, T., Yamamoto, T., Kawamoto, T., Kato, T., Sato, K., et al. (1991). Expression of c-erbB-2 gene product in urinary bladder cancer. Journal of Urology, 145, 423–427.PubMed

65.

Sato, K., Moriyama, M., Mori, S., Saito, M., Watanuki, T., Terada, K., et al. (1992). An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma. Cancer, 70, 2493–2498.CrossRefPubMed

66.

Lipponen, P., & Eskelinen, M. (1994). Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. British Journal of Cancer, 69, 1120–1125.PubMed

67.

Chow, N. H., Chan, S. H., Tzai, T. S., Ho, C. L., & Liu, H. S. (2001). Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clinical Cancer Research, 7, 1957–1962.PubMed

68.

Memon, A. A., Sorensen, B. S., Melgard, P., Fokdal, L., Thykjaer, T., & Nexo, E. (2004). Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients. British Journal of Cancer, 91, 2034–2041.CrossRefPubMed

69.

Memon, A. A., Sorensen, B. S., Meldgaard, P., Fokdal, L., Thykjaer, T., & Nexo, E. (2006). The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients. British Journal of Cancer, 94, 1703–1709.PubMed

70.

Kassouf, W., Black, P. C., Tuziak, T., Bondaruk, J., Lee, S., Brown, G. A., et al. (2008). Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. Journal of Urology, 179, 353–358.CrossRefPubMed

71.

Jimenez, R. E., Hussain, M., Bianco, F. J., Jr., Vaishampayan, U., Tabazcka, P., Sakr, W. A., et al. (2001). Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clinical Cancer Research, 7, 2440–2447.PubMed

72.

Kruger, S., Weitsch, G., Buttner, H., Matthiensen, A., Bohmer, T., Marquardt, T., et al. (2002). HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. International Journal of Cancer, 102, 514–518.CrossRef

73.

Cheng, H. L., Trink, B., Tzai, T. S., Liu, H. S., Chan, S. H., Ho, C. L., et al. (2002). Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder: a comparison with p53 nuclear accumulation. Journal of Clinical Oncology, 20, 1544–1550.CrossRefPubMed

74.

Cheng, H. L., Liu, H. S., Lin, Y. J., Chen, H. H., Hsu, P. Y., Chang, T. Y., et al. (2005). Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. British Journal of Cancer, 92, 1906–1914.CrossRefPubMed

75.

Sanchez-Carbayo, M., Socci, N. D., Lozano, J. J., Haab, B. B., & Cordon-Cardo, C. (2006). Profiling bladder cancer using targeted antibody arrays. American Journal of Pathology, 168, 93–103.CrossRefPubMed

76.

Rieger-Christ, K. M., Cain, J. W., Braasch, J. W., Dugan, J. M., Silverman, M. L., Bouyounes, B., et al. (2001). Expression of classic cadherins type I in urothelial neoplastic progression. Human Pathology, 32, 18–23.CrossRefPubMed

77.

Rieger-Christ, K. M., Lee, P., Zagha, R., Kosakowski, M., Moinzadeh, A., Stoffel, J., et al. (2004). Novel expression of N-cadherin elicits in vitro bladder cell invasion via the Akt signaling pathway. Oncogene, 23, 4745–4753.CrossRefPubMed

78.

di Martino, E., L’Hote, C. G., Kennedy, W., Tomlinson, D. C., & Knowles, M. A. (2009). Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner. Oncogene (in press).

79.

Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G., Neumann, D., et al. (2003). LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Current Biology, 13, 2004–2008.CrossRefPubMed

80.

Shaw, R. J., Bardeesy, N., Manning, B. D., Lopez, L., Kosmatka, M., DePinho, R. A., et al. (2004). The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell, 6, 91–99.CrossRefPubMed

81.

Sommerhaug, R. G., & Mason, T. (1970). Peutz-Jeghers syndrome and ureteral polyposis. JAMA, 211, 120–122.CrossRefPubMed

82.

Sanchez-Cespedes, M. (2007). A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene, 26, 7825–7832.CrossRefPubMed

83.

Adley, B. P., Smith, N. D., Nayar, R., & Yang, X. J. (2006). Birt-Hogg-Dube syndrome: clinicopathologic findings and genetic alterations. Archives of Pathology and Laboratory Medicine, 130, 1865–1870.PubMed

84.

Engelman, J. A. (2009). Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nature Reviews Cancer, 9, 550–562.CrossRefPubMed

85.

Liu, P., Cheng, H., Roberts, T. M., & Zhao, J. J. (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nature Review Drug Discovery, 8, 627–644.CrossRef

86.

O’Reilly, K. E., Rojo, F., She, Q. B., Solit, D., Mills, G. B., Smith, D., et al. (2006). mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Research, 66, 1500–1508.CrossRefPubMed

87.

Hussain, M. H., MacVicar, G. R., Petrylak, D. P., Dunn, R. L., Vaishampayan, U., Lara, P. N., Jr., et al. (2007). Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II national cancer institute trial. Journal of Clinical Oncology, 25, 2218–2224.CrossRefPubMed

Title: Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer
Authors: Margaret A. Knowles
Fiona M. Platt
Rebecca L. Ross
Carolyn D. Hurst
Publication date: 01-12-2009
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 3-4/2009
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-009-9198-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3-4/2009

MicroRNA function in cancer: oncogene or a tumor suppressor?

The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette–Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder

Strategies for molecular expression profiling in bladder cancer

Preface

Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer

Biology of urothelial tumorigenesis: insights from genetically engineered mice

Keynote webinar | Spotlight on antibody–drug conjugates in cancer