Abstract

Objective of Study: Advances in genomics technologies allow us to investigate molecular heterogeneity in cancer. Recent studies have identified muscle invasive bladder cancer (MIBC) molecular subtypes that are enriched with clinically actionable features such as specific mutations, copy number aberrations (CNAs), or molecular markers. Here, we provide an overview and clinical implications of the molecular subtypes.

Recent Findings: Early studies using unsupervised clustering analyses in bladder cancer revealed that non-muscle invasive bladder cancer (NMIBC) is easily distinguished from MIBC, implying that there are at least two major molecular subtypes in bladder cancer that conform closely with the stage. Recent studies identified MIBC subtypes that resembled the basal and luminal intrinsic subtypes in breast cancer. Basal tumors are associated with advanced stage at presentation and shorter survival in the absence of neoadjuvant chemotherapy. They are enriched with the mutations of TP53 and RB1 and squamous feature. Basal tumors are subdivided into ‘immune infiltrated’ and ‘immune suppressed’ subsets. Immune infiltrated basal tumors are significantly enriched with the characteristics of CD8+ T cells and active IFN-gamma signaling. Luminal tumors are enriched with papillary histology and they also can be subdivided by the signature of fibroblast infiltration, genomic unitability and activating FGFR3 mutations. Importantly, these subtypes have different prognosis and various response to systemic chemotherapy and immunotherapy. If the clinical implication of the molecular subtypes is validated prospectively, this information will be incorporated into the decision making for the management of bladder cancer patients.

Speaker Bio

Dr. Woonyoung Choi is an Assistant Professor of Urology and Director of Genomics for the [Greenberg Bladder Cancer Institute] (https://www.hopkinsmedicine.org/greenberg-bladder-cancer-institute/) at Johns Hopkins University. Dr. Choi was trained as a postdoctoral fellow in the Cancer Genomics Core Laboratory at the University of Texas MD Anderson Cancer Center, then joined at the department of Urology at Johns Hopkins School of medicine to have played a leadership role in the management of the expression profiling facility. Her research is focused on defining the biological mechanisms underlying the molecular subtypes that are observed in bladder cancer, with the goal of developing new therapeutic interventions. Dr. Choi’s research on molecular subtypes has been published in high impact factor journals (Cancer Cell, Nature Review Urology, European Urology) and highly regarded in the bladder cancer research fields.