# Pharmacological Modulation of Mutant TP53 with Oncotargets Against Esophageal Cancer and Therapy Resistance

## TL;DR

This paper reviews oncotargets involved in esophageal cancer progression and therapy resistance, focusing on their interaction with mutant TP53 to guide new treatment strategies.

## Contribution

The paper highlights novel pharmacological insights into mutant TP53's role in modulating key oncotargets for esophageal cancer therapy.

## Key findings

- Cancer stem cells, RARs, PFK, LDH, and HIF-1α are key oncotargets in esophageal cancer progression and therapy resistance.
- Mutant TP53 interacts with these oncotargets to influence carcinogenesis and tumor behavior.
- Understanding these interactions could improve treatment precision and reduce therapy resistance in EC.

## Abstract

The prevalence and deaths from esophageal cancer (EC) have recently increased. Although therapeutic strategies depend on the EC stage and recurrence, such as surgical intervention, chemotherapy, radiation therapy, chemoradiation therapy, targeted therapy, and immunotherapy, a more effective and novel treatment for EC is still required. This review briefly describes and summarizes some insightful oncotargets involved in the metabolic modulation of EC, including (1) cancer stem cells (CSCs) for EC progression, poor prognosis, tumor recurrence, and therapy resistance; (2) retinoic acid receptors (RARs) for esophageal carcinogenesis and regeneration; (3) phosphofructokinase (PFK) for EC-reprogrammed glycolysis; (4) lactate dehydrogenase (LDH) as an EC peripheral blood biomarker; and (5) hypoxia-inducible factor-1 alpha (HIF-1α) for the tumor microenvironment under hypoxic conditions. Moreover, the aforementioned oncotargets can be modulated by mutant TP53 and have their own features in the carcinogenesis, differentiation, proliferation, and metastasis of EC. Thus, the clarification of pharmacological mechanisms regarding the interaction between mutant TP53 and the abovementioned oncotargets could provide precise and perspective opinions for minimizing prediction errors, reducing therapy resistance, and developing novel drugs against EC.