PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 overexpression has been reported in many cancers. PELP1 expression is an independent prognostic predictor of shorter breast cancer–specific survival and disease free interval.  Patients whose tumors had high levels of cytoplasmic PELP1 exhibited a tendency to respond poorly to tamoxifen   and PELP1 deregulated tumors respond to Src kinase and mTOR inhibitors.  Treatment of breast and ovarian cancer xenografts with liposomal PELP1–siRNA–DOPC formulations revealed that knockdown of PELP1 significantly reduce the tumor growth. These results provided initial proof that PELP1 is a bonafide therapeutic target. Emerging data support a central role for PELP1 and its direct protein–protein interactions in cancer progression. Since PELP1 lacks known enzymatic activity, drugs that target PELP1 interactions with other proteins should have clinical utility. Recent studies described an inhibitor (D2) that block PELP1 interactions with AR. Since PELP1 interacts with histone modifications and epigenetic enzymes, drugs targeting epigenetic modifier enzymes may be useful in targeting PELP1 deregulated tumors.