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Cancers
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Epidermal Growth Factor Receptor (EGFR) Signaling in Cancer
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Epidermal Growth Factor Receptor (EGFR) Signaling in Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 8402

Special Issue Editors

Dr. Paul J. Higgins

E-Mail Website
Guest Editor
Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA
Interests: EGFR transactivation; TGF-β signaling; gene regulation; tumor progression; fibroproliferative disease; EMT; skin cancer; cell motility; PAI-1
Special Issues, Collections and Topics in MDPI journals
Dr. Rohan Samarakoon

E-Mail Website
Guest Editor
Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA
Interests: Hippo signaling; renal fibrosis; kidney cancer; EGFR transactivation; Non-SMAD TGF-β pathway; tumor suppressor deregulation in fibrosis
Special Issues, Collections and Topics in MDPI journals
Dr. Marzia Di Donato

E-Mail Website
Guest Editor
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy
Interests: prostate cancer, cell migration and invasion; 3D cell models; tumor microenvironment; prostate carcinoma-associated fibroblasts; cell cycle, androgen receptor non-genomic actions; growth factor receptors; signal transduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The epidermal growth factor receptor (EGFR) is a major contributor to tumor development and progression as well as an important therapeutic target. The EGFR and its ligands are often over-expressed in human carcinomas. Amplification of the EGFR gene, mutations within the EGFR tyrosine kinase domain and aberrant signaling are common in human epithelial malignancies where they impact tumor cell proliferation, plasticity, survival, localized tissue invasion and metastasis. The EGF/EGFR axis is also involved in drug resistance and pathologic cross-talk with other growth factor signaling pathways to promote inflammatory, angiogenic, fibrotic and mechanical changes in the tumor microenvironment, facilitating oncogenic behavior. EGFR transactivation by various cytokines and growth factors further underscore the complexity of engaged networks that dictate tumor cell phenotype and may shed light on the basis for the limited clinical utility of available EGFR inhibitors in halting cancer progression. The purpose of this Special Issue is to explore the expanding diversity of mechanisms that regulate EGFR activation and signaling in human neoplasms that may provide new opportunities for personalized anti-cancer therapy. We welcome submission of both review and original research articles for inclusion in this Special Issue by September 15, 2022

Dr. Paul J. Higgins
Dr. Rohan Samarakoon
Dr. Marzia Di Donato
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • GFR in human cancer
  • EGFR in tumor progression
  • EGF/EGFR signaling
  • EGFR mutations
  • EGFR pathway cross talk
  • EGFR transactivation
  • EGFR inhibitors
  • drug resistance

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Published Papers (3 papers)

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Research

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18 pages, 4169 KiB  
Article
Identification of EGFR-Related LINC00460/mir-338-3p/MCM4 Regulatory Axis as Diagnostic and Prognostic Biomarker of Lung Adenocarcinoma Based on Comprehensive Bioinformatics Analysis and Experimental Validation
by Mingxi Jia, Shanshan Feng, Fengxi Cao, Jing Deng, Wen Li, Wangyan Zhou, Xiang Liu and Weidong Bai
Cancers 2022, 14(20), 5073; https://doi.org/10.3390/cancers14205073 - 17 Oct 2022
Cited by 3 | Viewed by 1757
Abstract
Background: Lung adenocarcinoma (LUAD) is one of the most aggressive and lethal tumor types and requires effective diagnostic and therapeutic targets. Though the epidermal growth factor receptor (EGFR) is an important target for LUAD therapy, acquired resistance is still inevitable. In recent years, [...] Read more.
Background: Lung adenocarcinoma (LUAD) is one of the most aggressive and lethal tumor types and requires effective diagnostic and therapeutic targets. Though the epidermal growth factor receptor (EGFR) is an important target for LUAD therapy, acquired resistance is still inevitable. In recent years, the regulation of the EGFR by competing endogenous RNAs (ceRNAs) has been extensively studied and significant progress has been made. Therefore, we aim to find new targets for the diagnosis and treatment of LUAD by analyzing the EGFR-related ceRNA network in LUAD and expect to address the problem of EGFR resistance. Methods: We identified differentially expressed lncRNAs, miRNAs and mRNAs closely associated with the EGFR by analyzing transcriptome data from LUAD samples. Comprehensive bioinformatics analysis strongly suggests that the LINC00460—mir-338-3p—MCM4 ceRNA network plays an important role in the diagnosis and prognosis of LUAD. The effects of different patterns of the LINC00460/MCM4 axis on the overall survival of patients with LUAD were analyzed by a polygene regulation model. We also verified the expression of these genes in LUAD cell lines and tumor tissues by RT-PCR and immunohistochemistry. The functional enrichment analysis and targeted drug prediction of the MCM4 gene were performed. Results: Survival analysis indicated that high expressions of LINC00460 and MCM4 predict a shorter survival period for patients. Univariate and multivariate regression analyses demonstrated that higher expressions of LINC00460 and MCM4 were significantly associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. A multi-gene regulation model analysis revealed that the LINC00460 (downregulation)—mir-338-3p (upregulation)—MCM4 (downregulation) pattern significantly improved the overall survival of LUAD patients (p = 0.0093). RT-PCR and immunohistochemical experiments confirmed our analytical results. In addition, the functional enrichment analysis indicated that MCM4-related genes were mainly enriched in the cell cycle and cell division. A functional association network analysis showed that MCM4 was closely related to the EGFR. Finally, the possible targeted drugs of MCM4 were queried through the drug database platform, hoping to solve its drug resistance problem by targeting EGFR-related genes. Conclusions: In summary, the LINC00460/MCM4 axis can be used as a potential new perspective for targeting EGFR genes in precision medicine and is expected to serve as a diagnostic, prognostic and drug target for LUAD. Full article
(This article belongs to the Special Issue Epidermal Growth Factor Receptor (EGFR) Signaling in Cancer)
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18 pages, 2464 KiB  
Article
The Role of Curcumin in Prostate Cancer Cells and Derived Spheroids
by Mariarosaria Boccellino, Pasqualina Ambrosio, Andrea Ballini, Danila De Vito, Salvatore Scacco, Stefania Cantore, Antonia Feola, Marzia Di Donato, Lucio Quagliuolo, Antonella Sciarra, Giovanni Galasso, Felice Crocetto, Ciro Imbimbo, Silvia Boffo, Erika Di Zazzo and Marina Di Domenico
Cancers 2022, 14(14), 3348; https://doi.org/10.3390/cancers14143348 - 9 Jul 2022
Cited by 17 | Viewed by 3139
Abstract
A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were [...] Read more.
A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially available nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moderate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids. Full article
(This article belongs to the Special Issue Epidermal Growth Factor Receptor (EGFR) Signaling in Cancer)
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Review

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25 pages, 4927 KiB  
Review
Agri-Food By-Products in Cancer: New Targets and Strategies
by Carmela Sorrentino, Martina Di Gisi, Giulia Gentile, Fabrizio Licitra, Rosa D’Angiolo, Pia Giovannelli, Antimo Migliaccio, Gabriella Castoria and Marzia Di Donato
Cancers 2022, 14(22), 5517; https://doi.org/10.3390/cancers14225517 - 10 Nov 2022
Cited by 9 | Viewed by 2678
Abstract
The globalization and the changes in consumer lifestyles are forcing us to face a deep transformation in food demand and in the organization of the entire food production system. In this new era, the food-loss and food-waste security nexus is relevant in the [...] Read more.
The globalization and the changes in consumer lifestyles are forcing us to face a deep transformation in food demand and in the organization of the entire food production system. In this new era, the food-loss and food-waste security nexus is relevant in the global debate and avoiding unsustainable waste in agri-food systems as well as the supply chain is a big challenge. “Food waste” is useful for the recovery of its valuable components, thus it can assume the connotation of a “food by-product”. Sustainable utilization of agri-food waste by-products provides a great opportunity. Increasing evidence shows that agri-food by-products are a source of different bioactive molecules that lower the inflammatory state and, hence, the aggressiveness of several proliferative diseases. This review aims to summarize the effects of agri-food by-products derivatives, already recognized as promising therapeutics in human diseases, including different cancer types, such as breast, prostate, and colorectal cancer. Here, we examine products modulating or interfering in the signaling mediated by the epidermal growth factor receptor. Full article
(This article belongs to the Special Issue Epidermal Growth Factor Receptor (EGFR) Signaling in Cancer)
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