cAMP response element–binding protein: A credible cancer drug target

Despite advancements in radiotherapy, chemotherapy, endocrine therapy, targeted therapy and immunotherapy, resistance to therapy remains a pervasive challenge in oncology, in part owing to tumour heterogeneity. Identifying new therapeutic targets is key to addressing this challenge, as it can both diversify and enhance existing treatment options, particularly through combination regimens. The cAMP response element binding protein (CREB) is a transcription factor involved in various biological processes. It is aberrantly activated in several aggressive cancer types, including breast cancer. Clinically, high CREB expression is associated with increased breast tumour aggressiveness and poor prognosis. Functionally, CREB promotes breast cancer cell proliferation, survival, invasion, metastasis, as well as therapy resistance by deregulating genes related to apoptosis, cell cycle and metabolism. Targeting CREB with small molecule inhibitors has demonstrated promise in preclinical studies. This review summarises the current understanding of CREB mechanisms and its potential as a therapeutic target.