Based on published data from our group, we also address challenges that need to be overcome to optimize PI3K inhibition in BLCA and enable its successful translation into the clinic.
We reveal an aggressive mutational landscape in metastatic bladder cancer with 95% of patients harboring deleterious alterations to <i>TP53, RB1</i>, or <i>MDM2</i>, and 70% harboring a mutation or disrupting rearrangement affecting chromatin modifiers such as <i>ARID1A</i> Targetable alterations in MAPK/ERK or PI3K/AKT/mTOR pathways were robustly detected, including amplification of <i>ERBB2</i> (20% of patients) and activating hotspot mutations in <i>PIK3C</i>A (20%), with the latter mutually exclusive to truncating mutations in <i>TSC1</i> A novel <i>FGFR3</i> gene fusion was identified in consecutive samples from one patient.<b>Conclusions:</b> Our study demonstrates that ctDNA provides a practical and cost-effective snapshot of driver gene status in metastatic bladder cancer.
We hypothesized that genetic variations in the PI3K-AKT-mTOR pathway may affect the survival in muscle invasive and metastatic bladder cancer (MiM-BC) patients.