Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-related mortality worldwide, with more than half of them occurred in China. Radiotherapy (RT) has been widely used for treating ESCC. However, radiation-induced DNA damage response (DDR) can promote the release of cytokines and chemokines, and triggers inflammatory reactions and changes in the tumor microenvironment (TME), thereby inhibiting the immune function and causing the invasion and metastasis of ESCC. Radioresistance is the major cause of disease progression and mortality in cancer, and it is associated with heterogeneity. Therefore, a better understanding of the radioresistance mechanisms may generate more reversal strategies to improve the cure rates and survival periods of ESCC patients. We mainly summarized the possible mechanisms of radioresistance in order to reveal new targets for ESCC therapy. Then we summarized and compared the current strategies to reverse radioresistance.

Survival benefit of combined immunotherapy and chemoradiotherapy in locally advanced unresectable esophageal cancer: an analysis based on the SEER database

“…The abscopal effect relies on the presence of T cells, and radiotherapy may induce T cell depletion by increasing PD-L1 expression through the cGAS-Sting pathway, contributing to immune escape, reducing the abscopal effect, and increasing resistance to radiotherapy ( 19 , 20 ). Blocking the PD-L1 receptor can reverse T cell depletion, maintaining T cell immune homeostasis, which, in turn, enhances the abscopal effect during radiotherapy and overcomes radiotherapy resistance ( 21 , 22 ). Furthermore, tumor resistance to radiotherapy is often linked to tumor hypoxia caused by vascular abnormalities or dysfunction.…”

NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases

“…In this paper, we reviewed the roles of NEDD4 and NEDD4L in various digestive diseases for the purpose of providing new strategies for the prevention and treatment of digestive diseases. Esophageal cancer is the seventh most common cancer worldwide and the sixth most common cause of cancer-related deaths [75,76]. Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with a high incidence [77,78].…”

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma

“…The PI3K/Akt pathway can be irregularly activated via several mechanisms, including various genomic alterations such as mutations in PTEN, Akt, and mTOR mechanism[ 7 , 71 , 96 , 97 ]. Dysregulation of the RTK signaling pathway is implicated in the malignant progression of ESCC, including metastasis[ 4 , 98 , 99 ].…”

“…This signaling pathway consists of several components, including Wnts, receptors (such as Frizzled, FZD and low-density lipoprotein receptor-related proteins, LRP), Dishevelled (Dsh/Dvl), β-catenin, glycogen synthase kinase 3β (GSK-3β), Axin, and APC (adenomatous polyposis coli). Research has shown that the Wnt/β-catenin signaling pathway is intricately linked with tumor development, partly as a significant contributor to the onset and metastasis of ESCC, including metastasis[ 98 , 110 ].…”