Dr. Slingerland’s research has provided insight into how cancers escape negative growth controls. Following her discovery of a key cell cycle inhibitor, p27, her lab demonstrated that p27 levels are reduced in up to 60% of common human cancers (breast, prostate, lung, ovarian and others) in association with poor patient prognosis. She also has shown that cell cycle inhibitors, p15 and p27, cooperate to cause G1 arrest by transforming growth factor–beta (TGF-beta) and that cancer cells lose responsiveness to TGF-beta through loss or deregulation of p27. Current work addresses how p27 function is impaired in human breast and other cancers. Dr. Slingerland has demonstrated that functional inactivation of p27 in human cancers can either occur through accelerated p27 degradation or through altered p27 phosphorylation leading to p27 mislocalization. She has shown that antiestrogen drugs require the cdk inhibitors, p21 and p27, to arrest breast cancer growth, and that oncogenic activation of mitogenic signaling via the Src and MAPK pathways deregulate p27 function causing tamoxifen resistance in breast cancer. Efforts to prevent or reverse hormone independent, antiestrogen-resistant breast cancer growth using MEK and Src inhibitors are under investigation in pre-clinical studies and clinical trials.