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Cancers
Special Issues
Targeted Therapy in Gastrointestinal Cancer
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Targeted Therapy in Gastrointestinal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 9961

Special Issue Editors

Dr. Wei Kang

E-Mail Website
Guest Editor
Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong 999077, China
Interests: Hippo-YAP pathway; gastric cancer; cancer-associated fibroblast; tumor microenvironment; druggable targets; prognostic and predictive biomarkers
Prof. Dr. Ka Fai To

E-Mail Website
Guest Editor
Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong 999077, China
Interests: gastrointestinal cancer; gene mutation; oncogenes; tumor evolution; secreted protein; molecular classification

Special Issue Information

Dear Colleagues,

Gastrointestinal (GI) cancer is a major cause of cancer-related mortality and appears to be a great challenge for cancer treatment. The most common types of GI cancer are colorectal, gastric, esophageal, pancreatic, and liver cancers. General treatments, including surgical techniques, chemoradiotherapies, and immunotherapies, have been developed expeditiously, but the overall 5-year survival rate of GI cancer patients in advanced-stage disease is still less than 15% due to rapid disease progression, metastasis, and treatment resistance. Targeted therapy involves using drugs that target specific oncogenes involved in the growth and spread of cancer cells. Several monoclonal antibodies and small molecule inhibitors (especially tyrosine kinase inhibitors) have been approved for clinical usage. However, one of the critical puzzles is the heterogeneity between individuals, which requires personalized therapies to achieve better treatment outcomes. Thus, it is imperative to improve the prognosis of GI cancer patients by delineating the molecular mechanisms of tumor progression and developing novel targeted therapies.

This Special Issue aims to allow authors from different research areas (such as tumor biology, immunology, microbiology, drug design and development, pharmacology, and bioinformatics) to focus on targeted therapy in GI cancer treatment, describe the discoveries of their research, and deliver novel insights. Original research articles and reviews are welcome for this Special Issue. Research areas may include (but are not limited to) the following: the molecular mechanisms of GI cancers, targeted therapy development, the identification of promising oncogenic targets, the role of the microbiome in tumor microenvironment remodeling,  and the prognosis of GI cancers.

We look forward to receiving your contributions.

Dr. Wei Kang
Prof. Dr. Ka Fai To
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 short 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

  • gastrointestinal cancer
  • tumor microenvironment
  • gut microbiome
  • molecular mechanism
  • cancer treatment
  • prognostic and predictive biomarker
  • therapeutic target
  • cancer prognosis
  • targeted therapy
  • targeted drug development

Published Papers (6 papers)

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Research

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23 pages, 19862 KiB  
Article
A Comprehensive Understanding of Post-Translational Modification of Sox2 via Acetylation and O-GlcNAcylation in Colorectal Cancer
by Yoojeong Seo, Dong Keon Kim, Jihye Park, Soo Jung Park, Jae Jun Park, Jae Hee Cheon and Tae Il Kim
Cancers 2024, 16(5), 1035; https://doi.org/10.3390/cancers16051035 - 03 Mar 2024
Viewed by 1053
Abstract
Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with [...] Read more.
Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2. LC-MS-based proteomics analysis identified HDAC4 and p300 as binding partners involved in the acetylation-mediated control of Sox2 expression in the nucleus. Sox2 K75 acetylation is mediated by the acetyltransferase activity of CBP/p300 and ACSS3. In SW620 cells, HDAC4 deacetylates K75 and is regulated by miR29a. O-GlcNAcylation on S246, in addition to K75 acetylation, also regulates Sox2 stability. These findings provide insights into the regulation of Sox2 through multiple post-translational modifications and pathways in CRC. Full article
(This article belongs to the Special Issue Targeted Therapy in Gastrointestinal Cancer)
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17 pages, 3067 KiB  
Article
MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11
by Elisa Martino, Anna Balestrieri, Francesca Aragona, Giovanna Bifulco, Luigi Mele, Giuseppe Campanile, Maria Luisa Balestrieri and Nunzia D’Onofrio
Cancers 2023, 15(17), 4342; https://doi.org/10.3390/cancers15174342 - 30 Aug 2023
Cited by 1 | Viewed by 1516
Abstract
Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, [...] Read more.
Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, we aim at investigating the molecular mechanisms and regulatory targets of miR-148a-3p in the CRC cell death mechanism(s). To this end, miR-148a-3p expression was evaluated in SW480 and SW620 cells and normal colon epithelial CCD 841 CoN cells with quantitative real-time polymerase chain reaction (qRT-PCR). Data reported a reduction of miR-148a-3p expression in SW480 and SW620 cells compared to non-tumor cells (p < 0.05). Overexpression of miR-148a selectively inhibited CRC cell viability (p < 0.001), while weakly affecting normal CCD 841 CoN cell survival (p < 0.05). At the cellular level, miR-148a-3p mimics promoted apoptotic cell death via caspase-3 activation (p < 0.001), accumulation of mitochondrial reactive oxygen species (ROS) (p < 0.001), and membrane depolarization (p < 0.001). Moreover, miR-148a-3p overexpression induced lipid peroxidation (p < 0.01), GPX4 downregulation (p < 0.01), and ferroptosis (p < 0.01), as revealed by intracellular and mitochondrial iron accumulation and ACSL4/TFRC/Ferritin modulation. In addition, levels of SLC7A11 mRNA and protein, the cellular targets of miR-148a-3p predicted by bioinformatic tools, were suppressed by miR-148a-3p’s overexpression. On the contrary, the downregulation of miR-148a-3p boosted SLC7A11 gene expression and suppressed ferroptosis. Together, these in vitro findings reveal that miR-148a-3p can function as a tumor suppressor in CRC by targeting SLC7A11 and activating ferroptosis, opening new perspectives for the rationale of therapeutic strategies through targeting the miR-148a-3p/SLC7A11 pathway. Full article
(This article belongs to the Special Issue Targeted Therapy in Gastrointestinal Cancer)
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Review

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21 pages, 1348 KiB  
Review
Molecular Landscape and Therapeutic Strategies against Colorectal Cancer
by Aakash Patel and Pat Gulhati
Cancers 2024, 16(8), 1551; https://doi.org/10.3390/cancers16081551 - 18 Apr 2024
Viewed by 643
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Although the overall incidence of CRC is decreasing, the incidence of young-onset CRC, characterized by a diagnosis of CRC before age 50, is increasing. Outcomes for CRC patients are improving, partly [...] Read more.
Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Although the overall incidence of CRC is decreasing, the incidence of young-onset CRC, characterized by a diagnosis of CRC before age 50, is increasing. Outcomes for CRC patients are improving, partly due to comprehensive molecular characterization of tumors and novel therapeutic strategies. Advances in genomic and transcriptomic analyses using blood- and tumor-tissue-based sequencing have facilitated identification of distinct tumor subtypes harboring unique biological characteristics and therapeutic vulnerabilities. These insights have led to the development and incorporation of targeted therapies and immunotherapy in CRC treatment. In this review, we discuss the molecular landscape and key oncogenes/tumor suppressors contributing to CRC tumorigenesis, metastasis, and therapeutic resistance. We also discuss personalized therapeutic strategies for subsets of CRC patients and provide an overview of evolving novel treatments being evaluated in clinical trials. Full article
(This article belongs to the Special Issue Targeted Therapy in Gastrointestinal Cancer)
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16 pages, 690 KiB  
Review
Claudins—Promising Biomarkers for Selected Gastrointestinal (GI) Malignancies?
by Marta Łukaszewicz-Zając and Barbara Mroczko
Cancers 2024, 16(1), 152; https://doi.org/10.3390/cancers16010152 - 28 Dec 2023
Viewed by 719
Abstract
Despite recent(最近) improvements in diagnostic ability(能力) and treatment(治疗) strategies for patients(病人) with neoplastic disease(疾病), gastrointestinal (GI) cancers(癌症), such(这样) as colorectal, gastric, pancreatic, and oesophageal cancers(癌症), are still common(常见) malignancies and the leading(领先) cause(原因) of cancer(癌症) deaths worldwide(全世界), with a high frequency of recurrence [...] Read more.
Despite recent(最近) improvements in diagnostic ability(能力) and treatment(治疗) strategies for patients(病人) with neoplastic disease(疾病), gastrointestinal (GI) cancers(癌症), such(这样) as colorectal, gastric, pancreatic, and oesophageal cancers(癌症), are still common(常见) malignancies and the leading(领先) cause(原因) of cancer(癌症) deaths worldwide(全世界), with a high frequency of recurrence and metastasis as well as poor patient(病人) prognosis. There is a link(链接) between the secretion of proteolytic enzymes that degrade the extracellular matrix and the pathogenesis of GI tumours. Recent(最近) findings have focused(焦点) on the potential(潜在) significance(意义) of selected claudins (CLDNs) in the pathogenesis and prognosis of GI cancers(癌症). Tight junctions (TJs) have been proven to play an important role(作用) in maintaining cell(细胞) polarity and permeability. A number of authors have recently(最近) revealed that TJ proteins, particularly(特别是) selected CLDNs, are related(相关) to inflammation and the development(发展) of various tumours, including GI malignancies. This review(检讨) presents general(一般) characteristics and the involvement(参与) of selected CLDNs in the progression(进展) of GI malignancies, with a focus(焦点) on the potential(潜在) application(应用) of these proteins in the diagnosis(诊断) and prognosis of colorectal cancer(癌症) (CRC), gastric cancer(癌症) (GC), pancreatic cancer(癌症) (PC), and oesophageal cancer(癌症) (EC). Our review(检讨) indicates that selected CLDNs, particularly(特别是) CLDN1, 2, 4, 7, and 18, play a significant(显著) role(作用) in the development(发展) of GI tumours and in patient(病人) prognosis. Furthermore, selected CLDNs may be of value(价值) in the design(设计) of therapeutic(治疗) strategies for the treatment(治疗) of recurrent tumours. Full article
(This article belongs to the Special Issue Targeted Therapy in Gastrointestinal Cancer)
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25 pages, 1504 KiB  
Review
Exploring the Microbiome in Gastric Cancer: Assessing Potential Implications and Contextualizing Microorganisms beyond H. pylori and Epstein-Barr Virus
by Wing Sum Shin, Fuda Xie, Bonan Chen, Jun Yu, Kwok Wai Lo, Gary M. K. Tse, Ka Fai To and Wei Kang
Cancers 2023, 15(20), 4993; https://doi.org/10.3390/cancers15204993 - 15 Oct 2023
Cited by 1 | Viewed by 1628
Abstract
While previous research has primarily focused on the impact of H. pylori and Epstein-Barr virus (EBV), emerging evidence suggests that other microbial influences, including viral and fungal infections, may also contribute to gastric cancer (GC) development. The intricate interactions between these microbes and [...] Read more.
While previous research has primarily focused on the impact of H. pylori and Epstein-Barr virus (EBV), emerging evidence suggests that other microbial influences, including viral and fungal infections, may also contribute to gastric cancer (GC) development. The intricate interactions between these microbes and the host’s immune response provide a more comprehensive understanding of gastric cancer pathogenesis, diagnosis, and treatment. The review highlights the roles of established players such as H. pylori and EBV and the potential impacts of gut bacteria, mainly Lactobacillus, Streptococcus, hepatitis B virus, hepatitis C virus, and fungi such as Candida albicans. Advanced sequencing technologies offer unprecedented insights into the complexities of the gastric microbiome, from microbial diversity to potential diagnostic applications. Furthermore, the review highlights the potential for advanced GC diagnosis and therapies through a better understanding of the gut microbiome. Full article
(This article belongs to the Special Issue Targeted Therapy in Gastrointestinal Cancer)
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22 pages, 2386 KiB  
Review
Updated Epidemiology of Gastric Cancer in Asia: Decreased Incidence but Still a Big Challenge
by Wing Sum Shin, Fuda Xie, Bonan Chen, Peiyao Yu, Jun Yu, Ka Fai To and Wei Kang
Cancers 2023, 15(9), 2639; https://doi.org/10.3390/cancers15092639 - 06 May 2023
Cited by 10 | Viewed by 3794
Abstract
Despite the decline in incidence and mortality rates, gastric cancer (GC) is the fifth leading cause of cancer deaths worldwide. The incidence and mortality of GC are exceptionally high in Asia due to high H. pylori infection, dietary habits, smoking behaviors, and heavy [...] Read more.
Despite the decline in incidence and mortality rates, gastric cancer (GC) is the fifth leading cause of cancer deaths worldwide. The incidence and mortality of GC are exceptionally high in Asia due to high H. pylori infection, dietary habits, smoking behaviors, and heavy alcohol consumption. In Asia, males are more susceptible to developing GC than females. Variations in H. pylori strains and prevalence rates may contribute to the differences in incidence and mortality rates across Asian countries. Large-scale H. pylori eradication was one of the effective ways to reduce GC incidences. Treatment methods and clinical trials have evolved, but the 5-year survival rate of advanced GC is still low. Efforts should be put towards large-scale screening and early diagnosis, precision medicine, and deep mechanism studies on the interplay of GC cells and microenvironments for dealing with peritoneal metastasis and prolonging patients’ survival. Full article
(This article belongs to the Special Issue Targeted Therapy in Gastrointestinal Cancer)
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