Please enable JavaScript or talk to your local administrator to get JavaScript enabled.

Project

Identifying Predictors of Response to mTOR-targeted Therapies in Bladder Cancer

Funder: Bladder Cancer Advocacy Network

Funding period
USD 100 K
Funding amount
Abstract
Bladder cancer is the fifth most common cancer in the United States with over 70,000 cases diagnosed annually. While surgery with perioperative chemotherapy remains the standard of care for muscle-invasive disease, half of these patients experience metastatic recurrences, for which no standard of care exists. In a clinical trial of everolimus in metastatic bladder cancer, we identified a patient who exhibited a complete response to therapy. Whole genome sequencing identified Tuberous Sclerosis 1 (TSC1) loss as a contributor to this response; additional patients with TSC1 altered tumors experienced variable responses to everolimus. We hypothesize that the variability in response is related to the profile of co-altered genes in TSC1 mutant tumors. Although the rate of TSC1 alterations in bladder cancer is 10%, mTOR inhibitors are readily available for testing in this patient population and an improved understanding of this tumor subset will pave the way to more effective treatments for this disease. Therefore, we seek to genetically and functionally characterize TSC1 null bladder tumors using a multiplatform approach: Next Generation exon capture sequencing to define the prevalence of TSC1 alterations in a prospective cohort of invasive bladder tumors and the pattern of co-altered genes within these tumors; mouse models with urothelium-specific loss of TSC1 and TP53 (commonly altered with TSC1 in bladder cancer); and to explore the role of the chromatin modifying gene KDM6A, co-altered in half of TSC1 mutant tumors in the bladder TCGA, in bladder tumor progression in TSC1 expressing and null cell lines.
Similar projects All >
Sorted by: Start Date
Project list item
Characterization of Nectin-4 expression in molecular subtypes of urothelial cancer and mechanisms of resistance to enfortumab vedotin

Bladder Cancer Advocacy Network to Carissa Ellen Chu

USD 1,700
2020 - 2020
Project list item
Epigenetic regulators of subtype plasticity in bladder cancer

Bladder Cancer Advocacy Network to John Robert Christin

USD 1,700
2020 - 2020
Project list item
Defining NRF2 induced tumor invasion in bladder cancer

Bladder Cancer Advocacy Network to Yuki Kita, William Youngkwan Kim, Bernard Weissman

USD 50,000
2020 - 2021
Project list item
Implication of neutrophil extracellular traps in the efficacy of bladder-sparing therapy in muscle invasive bladder cancer

Canadian Institutes of Health Research to Wassim Kassouf, Jonathan David Spicer, Ciriaco A. Piccirillo

USD 138,878
2020 - 2025
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer

National Cancer Institute to NINA BHARDWAJ, JUN ZHU, MATTHEW GALSKY

USD 703,400
2020 - 2025

System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Human Genome

  • RCDC

    Tuberous Sclerosis

  • RCDC

    Brain Disorders

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Genetics

  • RCDC

    Rare Diseases

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Clinical

  • Broad Research Areas

    Basic Science