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Project

Unravelling Mechanisms of Resistance to Checkpoint Inhibition in Canine Urothelial Carcinoma

Funder: V Foundation for Cancer Research

Funding period
USD 500 K
Funding amount
Abstract
Approximately 80,000 Americans will be diagnosed with bladder cancer in 2019 and 18,000 will die from their disease this year. Recent studies show that bladder cancer cells often carry a high number of genetic mutations which correlate with anti-tumor immune responses. New drugs known as immune checkpoint inhibitors (ICI), have produce dramatic clinical responses in up to 25% of bladder cancer patients, by enhancing anti-tumor immune responses that help control the tumor. However, despite intense efforts, biomarkers that predict response to ICI remain elusive. Furthermore, the mechanisms responsible for resistance to ICI are unknown. Predicting which patients respond to ICI would enable responders to be streamlined to receive ICIs, and resistant patients to receive alternative or combination therapies to improve their outcome. Pet dogs also develop bladder cancer that shares similar clinical, biological and genetic features with human bladder cancer. Despite standard of care treatment, most dogs will die of their disease within one year of diagnosis. Here we will investigate the genetic mutational burden in canine bladder cancer and determine whether it also correlates with tumor immune profiles. We will develop a canine ICI that can be used therapeutically in dogs with bladder cancer and we will determine whether effective ICI therapy is associated with enhanced anti-tumor immune responses and which factors or combination of factors predict ICI response. This work aims to establish the dog as a valuable model for human bladder cancer, provide a novel treatment for these dogs and guide biomarker discovery for humans.
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System

Categories
  • FOR (ANZSRC)

    1107 Immunology

  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Genetics

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science