subculture-cryopreservation-esophageal-adenocarcinoma-organoids-pros

Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion

The lack of suitable translational research models reflecting primary disease to explore tumorigenesis and therapeutic strategies is a major obstacle in ...

University Hospital Cologne

Neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by surgery are two standard strategies in treating locally advanced esophageal cancer (EC). We aim to compare NCRT and NCT in the management of locally advanced EC patients.

Comparison of outcomes between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in patients with locally advanced esophageal cancer: A network meta-analysis.

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.

Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer.

Metabolism rewiring is an important hallmark of cancers. Being one of the most abundant free amino acids in the human blood, glutamine supports bioenergetics and biosynthesis, tumor growth, and the production of antioxidants through glutaminolysis in cancers. In glutamine dependent cancer cells, more than half of the tricarboxylic/critic acid (TCA) metabolites are derived from glutamine. Glutaminolysis controls the process of converting glutamine into TCA cycle metabolites through the regulation of multiple enzymes, among which the glutaminase shows the importance as the very first step in this process. Targeting glutaminolysis  glutaminase inhibition emerges as a promising strategy to disrupt cancer metabolism and tumor progression. Here, we review the regulation of glutaminase and the role of glutaminase in cancer metabolism and metastasis. Furthermore, we highlight the glutaminase inhibitor based metabolic therapy strategy and their potential applications in clinical scenarios.

Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies.

Esophageal adenocarcinoma (EAC) is one of the most lethal malignancies, and limits promising treatments. AKR1C3 represents a therapeutic target to combat the resistance in many cancers. However, the molecular mechanism of AKR1C3 in the chemotherapy resistance of EAC is still unclear. We found that the mRNA level of AKR1C3 was higher in EAC tumor tissues, and that high AKR1C3 expression might be associated with poor overall survival of EAC patients. AKR1C3 overexpression decreased cell death induced by chemotherapeutics, while knockdown of AKR1C3 attenuated the effect. Furthermore, we found AKR1C3 was inversely correlated with ROS production. Antioxidant NAC rescued chemotherapy-induced apoptosis in AKR1C3 knockdown cells, while the GSH biosynthesis inhibitor BSO reversed a protective effect of AKR1C3 against chemotherapy. AKT phosphorylation was regulated by AKR1C3 and might be responsible for eliminating over-produced ROS in EAC cells. Intracellular GSH levels were modulated by AKR1C3 and the inhibition of AKT could reduce GSH level in EAC cells. Here, we reported for the first time that AKR1C3 renders chemotherapy resistance through controlling ROS levels via AKT signaling in EAC cells. Targeting AKR1C3 may represent a novel strategy to sensitize EAC cells to conventional chemotherapy.

Article	Year
Comparison of outcomes between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in patients with locally advanced esophageal cancer: A network meta-analysis. EClinicalMedicine\| PubMed ID: 34805809	2021
Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer. Cells\| PubMed ID: 32560537	2020
Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies. Frontiers in oncology\| PubMed ID: 33194749	2020
Aldo-Keto Reductase 1C3 Mediates Chemotherapy Resistance in Esophageal Adenocarcinoma via ROS Detoxification. Cancers\| PubMed ID: 34065695	2021

Ningbo Fan

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