JCSMR School Seminar Series: Molecular subsets of muscle-invasive bladder cancer: implications for prognosis and therapy

Professor David McConkey, Professor of Urology and Cancer Biology, Director for Urological Research, and Deputy Division Head for Research (Surgery) at the University of Texas MD Anderson Cancer Center, Houston, US.

Using whole genome mRNA expression profiling of several cohorts of primary human tumors and unsupervised hierarchical cluster analyses, we identified 3 novel molecular subsets of muscle-invasive bladder cancer (MIBC). Basal MIBCs shared biomarkers with basal breast cancers, expressed an active EGFR-STAT3-ΔNp63a transcriptional network and EMT markers, and were enriched for squamous differentiation. Patients with basal cancers had late stage and metastatic disease at presentation. Luminal MIBCs were characterized by active estrogen receptor (ER) and PPARg signaling, luminal breast differentiation markers and activating FGFR3 mutations. The third subset was characterized by active p53/tumor suppressor pathway activation, and these p53-like primary tumors were consistently resistant to frontline neoadjuvant cisplatin-based combination chemotherapy. The unexpected observation that bladder and breast cancers share significant features has important implications for prognostication and the development of targeted therapies, and patients with p53-like MIBCs should not be treated with frontline cisplatin-based chemotherapy.

Dr David J McConkey is a Professor of Urology and Cancer Biology, Director for Urological Research, and Deputy Division Head for Research (Surgery) at the University of Texas MD Anderson Cancer Center. He received his BA in Biochemistry and American History from Brown University and his PhD from the Karolinska Institute in Stockholm. He performed postdoctoral studies in immunobiology at the Dana-Farber Cancer Institute before accepting a tenure-track position at MD Anderson in 1993. He has been studying the biochemical and molecular regulation of apoptosis since he was a graduate student, but more recently his work has focused on translational cancer research and the mechanisms of action of experimental therapeutics, particularly inhibitors of the proteasome and of growth factor receptors (EGFR and FGFRs). Dr McConkey has published almost 200 papers in peer-reviewed journals and is a Project Leader on the MD Anderson Specialized Programs of Research Excellence (SPORE) grant on bladder cancer.

Dr McConkey is on the editorial boards of Clinical Cancer Research, Molecular Cancer Therapeutics, and the Journal of Biological Chemistry and serves as a regular member of peer review panels for NCI. He is a member of several professional organizations including the American Urological Association, the Society for Basic Urological Research, the American Association for Cancer Research, and the American Society of Biochemistry and Molecular Biology. He is an active participant in The Cancer Genome Atlas (TCGA) Analysis Working Group, is on the Bladder Cancer Research Network (BCRN) Steering Committee, and is Chair for Translational Medicine on the Genitourinary Committee of the Southwest Oncology Group (SWOG).

Date & time

3–4pm 16 September 2013

Location

The Finkel Lecture Theatre, The John Curtin School of Medical Research, Building 131, Garran Road, ANU

Contacts

 Laura Vitler
 02 6125 2589

Updated:  18 October 2017/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager