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Project

Identifying Genomic Determinants of Chemoradiotherapy Response in Muscle-Invasive Bladder Cancer

Funder: Bladder Cancer Advocacy Network

Funding period
USD 50 K
Funding amount
Abstract
Combined modality therapy (CMT) involving concurrent chemotherapy and radiation is used in an organ-sparing approach for the treatment of muscle-invasive bladder cancer (MIBC) and can provide similar disease control rates as cystectomy-based approaches in appropriately selected patients. Despite significant recent advances in understanding the genetic and molecular features of bladder tumors, no clinically validated biomarkers are currently used to stratify patients or inform therapy selection for MIBC. We hypothesize that characterizing the mutational landscape of large cohorts of CMT-treated MIBC tumors, and correlating these mutational features with clinical endpoints such as tumor response and patient outcomes, could identify relevant biomarkers and serve to inform treatment decisions for MIBC patients.To this end, we propose to perform targeted sequencing of 1000 cancer-related genes in a large cohort of MIBC patients treated with CMT. Leveraging the available genomic technologies available at our institutions, we aim to perform targeted sequencing of more than 200 MIBC cases treated over the past decade at our institution. This cohort represents one of the largest single-institution MIBC cohorts treated with CMT and contains detailed clinical data regarding treatment response and patient outcomes. We believe that interrogating the status of known cancer genes in a large cohort of primary MIBC tumors will provide a unique opportunity to identify and validate biomarkers that could provide important information regarding risk stratification and therapy selection in MIBC. In addition, residual tumors from the subset of patients who failed CMT and subsequently underwent cystectomy at our institution are available and will be sequenced in parallel with the primary tumors from these patients. We anticipate that comparing the genomic features of pre- and post-CMT tumors will provide a unique window into mechanisms of response and resistance to CMT.
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System

Categories
  • FOR (ANZSRC)

    0604 Genetics

  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Human Genome

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Genetics

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    4.1 Discovery and preclinical testing of markers and technologies

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science