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Special Issue Editors

Special Issue Information

Dear Colleagues,

The treatment of cancer patients and antitumor drug investigation have caused great financial burden on healthcare systems and the whole of society. In the past few decades, cancer research and treatment have switched to a TME-centric pattern. The tumor microenvironment is constituted of various specialized microenvironments including hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, mechanical microenvironment, and even microbiota; each specialized microenvironment has a close crosstalk with one other. The tumor microenvironment and drug repurposing are becoming hot topics. Drug repurposing, also known as drug repositioning, has accelerated the process and greatly reduced the cost of drug development. Metformin and thalidomide are two such successful cases. We sincerely welcome researchers working in this field to submit original research articles or reviews including, but not limited to, repurposed drugs for cancer treatments, the current status of drug repurposing, and approaches to identify a repurposed drugs candidate targeting the tumor microenvironment to this Special Issue: New Insights into Tumor Microenvironment and Drug Repurposing.

Prof. Dr. Weilin Jin
Guest Editors

Dr. Mingzhu Jin
Co-Guest Editor

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Keywords

tumor microenvironment
drug repurposing
drug development
immunotherapy
clinical trials
metabolism

Published Papers (2 papers)

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Research

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14 pages, 13351 KiB

Open AccessArticle

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells

by Patricia Nefertari Ramírez-Flores, Paulina J. Barraza-Reyna, Alain Aguirre-Vázquez, María E. Camacho-Moll, Carlos Enrique Guerrero-Beltrán, Diana Resendez-Pérez, Vianey González-Villasana, Jesús Norberto Garza-González, Beatriz Silva-Ramírez, Fabiola Castorena-Torres and Mario Bermúdez de León

Molecules 2021, 26(19), 5742; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26195742 - 22 Sep 2021

Cited by 2 | Viewed by 2109

Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC. Full article

(This article belongs to the Special Issue New Insights into Tumor Microenvironment and Drug Repurposing)

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Review

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21 pages, 1592 KiB

Open AccessReview

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

by Zhi-Jian Han, Yang-Bing Li, Lu-Xi Yang, Hui-Juan Cheng, Xin Liu and Hao Chen

Molecules 2022, 27(1), 137; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27010137 - 27 Dec 2021

Cited by 41 | Viewed by 5858

Abstract

In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies. Full article

(This article belongs to the Special Issue New Insights into Tumor Microenvironment and Drug Repurposing)

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