Abstract
Treatment of muscle invasive urothelial bladder carcinoma (BCa) remains a major challenge. Comprehensive genomic profiling of tumors and identification of driver mutations may reveal new therapeutic targets. This manuscript discusses relevant molecular drivers of the malignant phenotype and agents with therapeutic potential in BCa. Small molecule pan-FGFR inhibitors have shown encouraging efficacy and safety results especially among patients with activating FGFR mutations or translocations. mTOR inhibitors for patients with TSC1 mutations and concomitant targeting of PI3K and MEK represent strategies to block PI3K/AKT/mTOR pathway. Encouraging preclinical results with ado-trastuzumab emtansine (T-DM1) exemplifies a new potential treatment for HER2-positive BCa along with innovative bispecific antibodies. Inhibitors of cell cycle regulators (aurora kinase, polo-like kinase 1, and cyclin-dependent kinase 4) are being investigated in combination with chemotherapy. Early results of clinical studies with anti-CTLA4 and anti-PDL1 are propelling immune modulating drugs to the forefront of emerging treatments for BCa. Collectively, these novel therapeutic targets and treatment strategies hold promise to improve the outcome of patients afflicted with this malignancy.
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