Resistance to chemotherapy and hormone therapy in endometrial cancer

Abstract

Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo-and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.

p21-activated kinase 4 regulation of endometrial cancer cell migration and invasion involves the ERK1/2 pathway mediated MMP-2 secretion

“…Further studies are needed to elucidate the mechanisms and effects of Pak4 on cell proliferation in short-term and longterm cultures. The efficacy of anticancer therapies depends not only on the cellular damage they cause but also on the cell's ability to respond to these damages by inducing the apoptotic response [42]. Although we observed that Pak4 had no significant effect on EC cell apoptosis under regular culture conditions, Pak4 was found to protect HeLa and NIH3T3 cells from apoptosis induced by TNF-α and UV irradiation [43,44].…”

Antitumor Activity of Ridaforolimus and Potential Cell-Cycle Determinants of Sensitivity in Sarcoma and Endometrial Cancer Models

“…Chemotherapy and hormonal therapy play important roles in first-line management of endometrial tumors; however, the majority of patients with advanced endometrial cancer relapse and face a dismal prognosis (20). Similarly, advanced and metastatic sarcoma is rarely curable, as standard chemotherapy has a low response rate, and consequently patient prognosis remains poor (21).…”

Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation

“…Endometrial cancer is the most common gynecological malignancy worldwide and represents the eighth leading cause of cancer-related deaths in women (1)(2)(3). Most endometrial adenocarcinomas are characterized by positive nuclear estrogen receptor (ER) expression and responsiveness to hormone stimulation.…”