Function of p21 and its therapeutic effects in esophageal cancer

Abstract

Esophageal cancer (EC) is the eighth most common type of cancer worldwide and ranks sixth among the causes of cancer-related mortality. Due to the high mortality rate and poor treatment efficacy for EC, millions of individuals succumb to this disease; thus, the identification of novel treatment targets is of utmost importance and urgency. In recent years, there have been advances if therapies targeting cell cycle regulators. p21 is a type of cell cycle regulator that plays a dual role in tumor cells, as it can not only regulate the cell cycle, induce apoptosis and inhibit cell proliferation, but can also protect cells from apoptosis. It has been found that p21 often exerts a tumor-suppressive effect on EC, which provides a basis for its use as a treatment target for EC. Therefore, the aim of the present study was to review the function of p21 and its potential value as a therapeutic target for EC.

Keywords: CDK4/6 inhibitors; esophageal cancer; p21; p53; targeted drugs.

Figure 1.

p21 combines with different cyclin-CDK complexes to exert its effects. CDK, cyclin-dependent kinase.

Figure 2.

p21 is regulated by multiple pathways. It was found that p21 is a key factor in esophageal cancer cells. Through the control of p21, the regulation of cell proliferation, senescence and apoptosis may be achieved. The pathway indicated by the black line has not been confirmed in esophageal cancer cells. The main purpose was to highlight the double-sidedness of p21, and this double-sidedness is often associated with the localization of p21 in the cell.

Figure 3.

A number of pathogenic factors are implicated in esophageal cancer. Hereditary and daily living habits are considered as the main carcinogenic factors. Barrett's esophagus is a high-risk factor for esophageal adenocarcinoma. Previous studies have demonstrated that a high expression of p21 is an indicator of a favorable prognosis for patients with esophageal cancer. Following treatment, the expression of p21 changes from negative to positive, which also indicates a favorable prognosis.