Role of FOXO protein's abnormal activation through PI3K/AKT pathway in platinum resistance of ovarian cancer

Abstract

Aim: Platinum-based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum-resistant ovarian cancer.

Methods: We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum-resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature.

Results: Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM-Chk2-p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum-resistant ovarian cancer cell model, it was found that FoxO-1 is decreased in platinum-resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum-induced apoptosis may further guide the treatment of platinum-resistant ovarian cancer.

Conclusions: There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re-understand the role that FOXOs have played in cancer development and treatment.

Keywords: FOXO; PI3K/AKT; apoptosis; ovarian cancer; platinum-resistance.