Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients

ERa36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated "nongenomic" signaling pathway. Membrane-initiated estrogen signaling has been linked to rapid responses to estrogen and generally activates signaling pathways like MAPK/ERK, phosphatidylinositol-3-kinase, and protein kinase C pathways. Preclinical study demonstrated that ERa36 was expressed in tumor cells and might be the driving force of breast cancer cell proliferation. 40% of breast cancer tumors which used to be considered as ER negative also express ERa36. In the former study the investigators found that 40% of ERa66-positive breast cancer patients express high levels of ERa36 in their tumors, and this subset of patients are less likely to benefit from tamoxifen treatment compared with those with ERa66-positive/ERa36-negative tumors. Icaritin is a newly discovered small molecular compound which is high selective ERa36 modulators and perhaps will be a very promising new drug to treat advanced breast cancer by targeting this nongenomic pathway. It was showed that it can inhibit the growth of breast cancer cells both in vitro and in vivo. The investigators have completed the preclinical PK\&PD and toxicity studies in animals and now move on to test it in a FIM clinical trial.