Analysis of the gene expression of cancers has resulted in the discovery of subtypes that cannot be differentiated by a pathologist examining them under a microscope. We have defined two novel subtypes of high-grade bladder cancer called “basal-like” and “luminal”. These subtypes have clear differences in survival (basal-like has worse overall survival) and very interestingly, the bladder subtypes strikingly reflect the luminal and basal-like molecular subtypes of breast cancer. We have defined a set of just 47 genes that can accurately classify luminal and basal-like bladder cancer, called the BASE47, and see that much like breast cancer, African Americans (AA) with bladder cancer appear to have a much higher incidence of the basal-like subtype. Based on the remarkable similarities between the bladder and breast intrinsic subtypes, we hypothesize that basal-like bladder cancer has unique epidemiologic associations as well as sensitivities to chemotherapy like basal-like breast cancer. In this proposal we will develop the BASE47 test to work on formalin-fixed, paraffin-embedded tissues (also called tumor blocks). This will allow the widespread use of the BASE47 test since most patients do not have fresh frozen tumor samples available to them. We will also determine the incidence of basal-like bladder cancer in AA and validate whether the basal-like subtype is more responsive to chemotherapy. Successful completion of the proposal would pave the way towards a clinically applicable test that could be performed to predict response to chemotherapy. Given that chemotherapy, while effective, is associated with significant toxicity in this older patient population (median age of diagnosis is 70), the development of the BASE47 as a predictive biomarker of chemotherapy response will be tremendously beneficial in maximizing chemotherapy use in patients most likely to respond while avoiding its use in others. Judicious use of the BASE47 will both increase chemotherapy’s effectiveness as well as improve the quality of life for this patient population. Finally, confirmation that AA are enriched in basal-like bladder cancer would not only suggest that a differing biology plays a role in the inferior outcomes of AA patients with bladder cancer but would also suggest that they may be particularly responsive to drugs targeting the basal-like subtype.
|Effective start/end date||1/1/15 → 12/31/18|
- American Cancer Society (ACS)
Urinary Bladder Neoplasms
Drug Delivery Systems
Quality of Life