Many patients with metastatic bladder cancer have inactivated SMARCB1, which is normally involved in DNA remodeling. The loss of SMARCB1 activates the STAT3 inflammation pathway and is a well-known biomarker of aggressive renal medullary carcinoma, suggesting that these events drive tumor growth and progression.
To provide further insights, researchers led by Pavlos Msaouel, M.D., Ph.D., used lab models of bladder cancer without SMARCB1. SMARCB1 deficiency led to increased STAT3 activation as well as increased tumor growth and metastasis. The researchers saw increased STAT3 activation in patients with bladder cancer and showed that treatment with a STAT3 inhibitor reduced tumor growth and metastasis in vivo, highlighting its therapeutic potential. The team also developed a novel gene expression signature to help identify SMARCB1-deficient patients most likely to benefit from STAT3 inhibitors, and they suggest it merits further clinical evaluation in this subset of patients.