The Phenotypically Suppressed Cancer Cell As a Therapeutic Target

Abstract

Bladder cancer recurs in up to 70% of patients judged to be tumor-free after treatment. Like other cancers, delayed appearance of metastases is common. These findings suggest the malignant phenotype can be suppressed, to emerge later. Following up on previous research in our laboratory showing that normal extracellular matrix can suppress the malignant phenotype of bladder cancers, we here demonstrate that the suppression of the malignant phenotype in culture models of bladder cancer cells grown on a gel derived from normal extracellular matrix also occurs in flank xenograft models. In addition, we also demonstrate a novel screening method to identify drugs that preferentially target suppressed bladder cancer cells that normally are resistant to conventional chemotherapeutic agents. This screening method could potentially identify completely novel therapeutic agents targeting the suppressed cancer cell and could be used to prevent recurrence and destroy potentially fatal micrometastatic tumors.