Actionable mutations in muscle-invasive bladder cancer

Thirty-five percent of bladder cancer patients either present with or develop muscle-invasive disease. The current standard of care for these patients is neoadjuvant chemotherapy followed by radical cystoprostatectomy or combined chemoradiotherapy. Despite these therapies, approximately 50% of patients will relapse after definitive locoregional treatment and eventually succumb to their disease.

Therapies targeted at altered genetic pathways have proven efficacy in localized solid tumors including breast cancer, head and neck cancer and GIST. No such treatments have proven clinical benefit in bladder cancer, but targets under active investigation include HER2, epidermal growth factor receptors, fibroblast growth factor receptor 3, mTOR and others. Efforts are also underway to genetically define the subgroup of patients, which benefit from systemic platinum-based chemotherapy in this setting.

Ongoing clinical trials are investigating the role of treatments targeted at actionable genetic mutations in bladder cancer. The key to maximizing the potential benefit from this treatment approach will be the identification of predictive biomarkers of response, the identification of safe combinations which block multiple signaling molecules synchronously, and the availability of faster, cheaper genetic testing in the clinic.