The Forkhead transcription factor FOXO1, an important downstream target of phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway, regulates cellular homeostasis by maintaining cell proliferation, apoptosis and viability in normal cells. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling, and is also central to the decision for a preadipocyte to commit to adipogenesis.

FOXO1 is broadly expressed in different types of cells with high level of expression in lymphoid cells and non-Hodgkin’s lymphomas. In contrast, in most of classical Hodgkin lymphoma (cHL), Reed-Sternberg cells are FOXO1 negative. A study investigated the role of PI3K inhibition on FOXO1 regulation in Cervical Cancer. Expression profiling of primary tumors and cell lines show over expression of PIK3CA and AKT1; and down regulation of FOXO1. It was concluded that activation of FOXO1 and its nuclear sequestration is critical in the regulation of cell proliferation, cell viability and apoptosis in Cervical Cancer. Hence, PI3K/AKT pathway may be a potential molecular target for cervical cancer therapy. Androgens and the androgen receptor (AR) are essential for growth and differentiation of the normal prostate gland as well as proliferation and survival of Prostate Cancer. FOXA1, functions as a pioneer factor to facilitate AR transactivation and Prostate Cancer growth. In contrast, the O-class of FOX proteins such as FOXO1 and FOXO3, which are downstream effectors of the PTEN tumor suppressor, inhibits the transcriptional activity of either full-length AR or constitutively active splice variants of AR in a direct or indirect manner in Prostate Cancer. Translocation of FOXO1 gene with PAX3 has been associated with alveolar rhabdomyosarcoma.