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Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 1 January 2025 | Viewed by 18477

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Dr. Liudmila V. Spirina

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Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia
Interests: oncogenesis; gastric cancer; colorectal cancer; biochemistry of cancers; molecular oncology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Irina V. Kondakova

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Laboratory of Tumor Biochemistry, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia
Interests: cancer; proteasomes; calpains; actin-binding proteins; survival prognosis
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Natalya V. Yunusova

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Laboratory of Tumor Biochemistry, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia
Interests: colorectal cancer; biochemistry of cancers; molecular oncology; exosomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The accumulated fundamental knowledge testifies the multiple complex molecular mechanisms in oncogenesis that determine the characteristics of disease progression and affect tumor responses to therapy. Tumor heterogeneity is a fact. Single attempts of cancer clustering using molecular and genetic approaches are adequate, but they are not applied in practical oncology. Increasing the effectiveness of antitumor measures is a significant task in practical oncology.

New techniques, targeted drugs, and chemotherapy regimens are not always successful due to inherited or acquired resistance to anti-cancer therapy. There is insufficient knowledge about molecular-based approaches in anti-cancer treatment. The main goal of the Special Issue is to summarize practical molecular-based methods in the therapy of gastric and colorectal cancers.

Dr. Liudmila V. Spirina
Prof. Dr. Irina V. Kondakova
Prof. Dr. Natalya V. Yunusova
Guest Editors

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Keywords

molecular-based therapy
gastric cancer
colorectal cancer
new anti-cancer targets
response to the therapy

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Published Papers (11 papers)

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Research

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31 pages, 5879 KiB

Open AccessArticle

Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue

by Błażej Ochman, Piotr Limanówka, Sylwia Mielcarska, Agnieszka Kula, Miriam Dawidowicz, Wiktor Wagner, Dorota Hudy, Monika Szrot, Jerzy Zbigniew Piecuch, Jerzy Piecuch, Zenon Czuba and Elżbieta Świętochowska

Curr. Issues Mol. Biol. 2024, 46(9), 10218-10248; https://doi.org/10.3390/cimb46090609 - 15 Sep 2024

Viewed by 1316

Abstract

Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate the expression of SEMA7A, SEMA4D, ADAM8, and ADAMTS10 in colorectal cancer (CRC) in relation to the mutational landscape of KRAS, NRAS, BRAF, PIK3CA, and AKT genes, microsatellite instability (MSI) status, and clinicopathological features. We also examined the associations between the expression of these proteins and selected cytokines, chemokines, and growth factors, assessed using a multiplex assay. Protein concentrations were quantified using ELISA in CRC tumors and tumor-free surgical margin tissue homogenates. Gene mutations were evaluated via RT-PCR, and MSI status was determined using immunohistochemistry (IHC). GSEA and statistical analyses were performed using R Studio. We observed a significantly elevated expression of SEMA7A in BRAF-mutant CRC tumors and an overexpression of ADAM8 in KRAS 12/13-mutant tumors. The expression of ADAMTS10 was decreased in PIK3CA-mutant CRC tumors. No significant differences in the expression of the examined proteins were observed based on MSI status. The SEMA7A and SEMA4D expressions were correlated with the expression of numerous cytokines associated with various immune processes. The potential immunomodulatory functions of these molecules and their suitability as therapeutic targets require further investigation. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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18 pages, 4450 KiB

Open AccessArticle

Erlotinib Treatment in Colorectal Cancer Suppresses Autophagy Based on KRAS Mutation

by Alexander Siegman, Aaron Shaykevich, Danbee Chae, Isaac Silverman, Sanjay Goel and Radhashree Maitra

Curr. Issues Mol. Biol. 2024, 46(7), 7530-7547; https://doi.org/10.3390/cimb46070447 - 16 Jul 2024

Cited by 1 | Viewed by 1086

Abstract

The KRAS gene is mutated in approximately 45% of colorectal cancer patients. There are currently very few targeted treatments or therapies equipped to directly inhibit KRAS due to its unusual structural intricacies. Erlotinib, an EGFR inhibitor, has previously been demonstrated to reduce cell viability by inducing autophagy in lung cancer cell lines with varying EGFR mutations. In contrast to lung cancer cells, evidence is provided herein for the first time that erlotinib treatment in colorectal cancer (CRC) cell lines reduces autophagy and still results in decreased cell viability. However, the effects of erlotinib in CRC cell lines containing a wildtype KRAS gene were different than in cells carrying a mutant KRAS gene. We show that there is significantly more downregulation of autophagy in KRAS mutant CRC cells compared to KRAS wildtype cells, both at transcriptional and translational levels, suggesting that the KRAS mutation is advantageous for cancer growth, even in the presence of erlotinib. Cell viability results determined that KRAS wildtype CRC cells had significantly more cell death compared to KRAS mutant cells. Using patient mRNA datasets, we showed that there was a significant correlation between the presence of the KRAS mutation and the expression of autophagy proteins. Additionally, through molecular dynamics simulations, we develop a blueprint for KRAS and autophagy protein interaction and the impact of the KRAS mutation on autophagy protein regulation. Overall, this is the first report of erlotinib treatment in CRC cells that assesses autophagy, and we demonstrate that autophagy activity is downregulated in these cells. This effect is not only greater in cells carrying a KRAS mutation compared to wildtype cells, but the KRAS mutant cells also have increased cell viability compared to wildtype cells. We hypothesize that the difference in cell viability and autophagy expression between KRAS mutant and KRAS wildtype cells after treatment with erlotinib can be of therapeutic value to treat CRC patients carrying KRAS mutations. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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18 pages, 11668 KiB

Open AccessArticle

Drug-Resistance Biomarkers in Patient-Derived Colorectal Cancer Organoid and Fibroblast Co-Culture System

by Kyoung-Bin Ryu, Jeong-ah Seo, Kyerim Lee, Juhyun Choi, Geon Yoo, Ji-hye Ha and Mee Ryung Ahn

Curr. Issues Mol. Biol. 2024, 46(6), 5794-5811; https://doi.org/10.3390/cimb46060346 - 11 Jun 2024

Viewed by 1762

Abstract

Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. We used an indirect co-culture system comprising colorectal cancer organoids and cancer-associated fibroblasts to simulate the tumor microenvironment. Immunofluorescence staining validated the characteristics of both organoids and fibroblasts, showing high expression of epithelial cell markers (EPCAM), colon cancer markers (CK20), proliferation markers (KI67), and fibroblast markers (VIM, SMA). Transcriptome profiling was conducted after treatment with anticancer drugs, such as 5-fluorouracil and oxaliplatin, to identify chemoresistance-related genes. Changes in gene expression in the co-cultured colorectal cancer organoids following anticancer drug treatment, compared to monocultured organoids, particularly in pathways related to interferon-alpha/beta signaling and major histocompatibility complex class II protein complex assembly, were identified. These two gene groups potentially mediate drug resistance associated with JAK/STAT signaling. The interaction between colorectal cancer organoids and fibroblasts crucially modulates the expression of genes related to drug resistance. These findings suggest that the interaction between colorectal cancer organoids and fibroblasts significantly influences gene expression related to drug resistance, highlighting potential biomarkers and therapeutic targets for overcoming chemoresistance. Enhanced understanding of the interactions between cancer cells and their microenvironment can lead to advancements in personalized medical research.. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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14 pages, 7061 KiB

Open AccessArticle

Colorectal Cancer Detection via Metabolites and Machine Learning

by Rachel Yang, Igor F. Tsigelny, Santosh Kesari and Valentina L. Kouznetsova

Curr. Issues Mol. Biol. 2024, 46(5), 4133-4146; https://doi.org/10.3390/cimb46050254 - 30 Apr 2024

Viewed by 1331

Abstract

Today, colorectal cancer (CRC) diagnosis is performed using colonoscopy, which is the current, most effective screening method. However, colonoscopy poses risks of harm to the patient and is an invasive process. Recent research has proven metabolomics as a potential, non-invasive detection method, which can use identified biomarkers to detect potential cancer in a patient’s body. The aim of this study is to develop a machine-learning (ML) model based on chemical descriptors that will recognize CRC-associated metabolites. We selected a set of metabolites found as the biomarkers of CRC, confirmed that they participate in cancer-related pathways, and used them for training a machine-learning model for the diagnostics of CRC. Using a set of selective metabolites and random compounds, we developed a range of ML models. The best performing ML model trained on Stage 0–2 CRC metabolite data predicted a metabolite class with 89.55% accuracy. The best performing ML model trained on Stage 3–4 CRC metabolite data predicted a metabolite class with 95.21% accuracy. Lastly, the best-performing ML model trained on Stage 0–4 CRC metabolite data predicted a metabolite class with 93.04% accuracy. These models were then tested on independent datasets, including random and unrelated-disease metabolites. In addition, six pathways related to these CRC metabolites were also distinguished: aminoacyl-tRNA biosynthesis; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; and alanine, aspartate, and glutamate metabolism. Thus, in this research study, we created machine-learning models based on metabolite-related descriptors that may be helpful in developing a non-invasive diagnosis method for CRC. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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9 pages, 2486 KiB

Open AccessCommunication

Anti-Prokineticin1 Suppresses Liver Metastatic Tumors in a Mouse Model of Colorectal Cancer with Liver Metastasis

by Hiroko Kono, Takanori Goi, Takayuki Matsunaka and Kenji Koneri

Curr. Issues Mol. Biol. 2024, 46(1), 44-52; https://doi.org/10.3390/cimb46010004 - 19 Dec 2023

Cited by 1 | Viewed by 1189

Abstract

Multidisciplinary treatment for colorectal cancer (CRC) has undergone significant advances, and molecularly targeted drugs have substantially improved patient prognosis. However, one problem with current molecularly targeted therapeutics is that they must be used in combination with anticancer agents. New molecular targeted therapies that can be used alone are needed. We have previously identified prokineticin1 (PROK1) factor as a therapeutic potential target for CRC. PROK1 factor is involved in the angiogenesis of tissues surrounding CRC tumors. Additionally, PROK1 receptors 1 and 2 are expressed in CRC cell lines, playing roles in cell proliferation via an autocrine mechanism and in the signaling system. In this study, a liver metastasis mouse model was developed using human colorectal cancer cell lines, and mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every three days. The number, size, and cell proliferation ability of metastatic lesions were analyzed. Our results suggested that the number, size, and cancer cell proliferation ability of metastatic lesions decreased, and the survival time significantly increased in the antibody-treated group compared to those in the control group. Thus, the anti-PROK1 antibody therapy suppressed the cell proliferation ability of liver metastatic lesions in a CRC mouse model, suggesting its potential as a novel treatment strategy. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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17 pages, 4967 KiB

Open AccessArticle

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)

by Héctor Herrera-Orozco, Verónica García-Castillo, Eduardo López-Urrutia, Antonio Daniel Martinez-Gutierrez, Eloy Pérez-Yepez, Oliver Millán-Catalán, David Cantú de León, César López-Camarillo, Nadia J. Jacobo-Herrera, Mauricio Rodríguez-Dorantes, Rosalío Ramos-Payán and Carlos Pérez-Plasencia

Curr. Issues Mol. Biol. 2023, 45(12), 9549-9565; https://doi.org/10.3390/cimb45120597 - 28 Nov 2023

Viewed by 1434

Abstract

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< −1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA–miRNA–mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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14 pages, 1633 KiB

Open AccessArticle

Targeting RAF Isoforms and Tumor Microenvironments in RAS or BRAF Mutant Colorectal Cancers with SJ-C1044 for Anti-Tumor Activity

by Sungpyo Hong, Myeongjin Jeon, Jeonghee Kwon, Hanbyeol Park, Goeun Lee, Kilwon Kim and Soonkil Ahn

Curr. Issues Mol. Biol. 2023, 45(7), 5865-5878; https://doi.org/10.3390/cimb45070371 - 13 Jul 2023

Cited by 3 | Viewed by 1864

Abstract

Colorectal cancer (CRC) is a significant global health issue characterized by a high prevalence of KRAS gene mutations. The RAS/MAPK pathway, involving KRAS, plays a crucial role in CRC progression. Although some RAS inhibitors have been approved, their efficacy in CRC is limited. To overcome these limitations, pan-RAF inhibitors targeting A-Raf, B-Raf, and C-Raf have emerged as promising therapeutic strategies. However, resistance to RAF inhibition and the presence of an immunosuppressive tumor microenvironment (TME) pose additional obstacles to effective therapy. Here, we evaluated the potential of a novel pan-RAF inhibitor, SJ-C1044, for targeting mutant KRAS-mediated signaling and inhibiting CRC cell proliferation. Notably, SJ-C1044 also exhibited inhibitory effects on immunokinases, specifically, CSF1R, VEGFR2, and TIE2, which play crucial roles in immune suppression. SJ-C1044 demonstrated potent antitumor activity in xenograft models of CRC harboring KRAS or BRAF mutations. Importantly, treatment with SJ-C1044 resulted in increased infiltration of T cells and reduced presence of tumor-associated macrophages and regulatory T cells within the TME. Thus, SJ-C1044 shows immunomodulatory potential and the ability to enhance antitumor responses. The study underscores the therapeutic potential of SJ-C1044 as a novel pan-RAF inhibitor capable of targeting oncogenic signaling pathways and overcoming immune suppression in CRC. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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19 pages, 10008 KiB

Open AccessArticle

Exploring Key Biomarkers and Common Pathogenesis of Seven Digestive System Cancers and Their Correlation with COVID-19

by Zuming Xiong, Yongjun Yang, Wenxin Li, Yirong Lin, Wei Huang and Sen Zhang

Curr. Issues Mol. Biol. 2023, 45(7), 5515-5533; https://doi.org/10.3390/cimb45070349 - 30 Jun 2023

Cited by 2 | Viewed by 2200

Abstract

Digestive system cancer and COVID-19 significantly affect the digestive system, but the mechanism of interaction between COVID-19 and the digestive system cancers has not been fully elucidated. We downloaded the gene expression of COVID-19 and seven digestive system cancers (oral, esophageal, gastric, colorectal, hepatocellular, bile duct, pancreatic) from GEO and identified hub differentially expressed genes. Multiple verifications, diagnostic efficacy, prognostic analysis, functional enrichment and related transcription factors of hub genes were explored. We identified 23 common DEGs for subsequent analysis. CytoHubba identified nine hub genes (CCNA2, CCNB1, CDKN3, ECT2, KIF14, KIF20A, KIF4A, NEK2, TTK). TCGA and GEO data validated the expression and excellent diagnostic and prognostic ability of hub genes. Functional analysis revealed that the processes of cell division and the cell cycle were essential in COVID-19 and digestive system cancers. Furthermore, six related transcription factors (E2F1, E2F3, E2F4, MYC, TP53, YBX1) were involved in hub gene regulation. Via in vitro experiments, CCNA2, CCNB1, and MYC expression was verified in 25 colorectal cancer tissue pairs. Our study revealed the key biomarks and common pathogenesis of digestive system cancers and COVID-19. These may provide new ideas for further mechanistic research. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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Review

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17 pages, 2540 KiB

Open AccessReview

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

by Wei Wu, Lei Zhu, Zhimin Dou, Qiliang Hou, Sen Wang, Ziqian Yuan and Bin Li

Curr. Issues Mol. Biol. 2024, 46(1), 948-964; https://doi.org/10.3390/cimb46010061 - 22 Jan 2024

Cited by 4 | Viewed by 2666

Abstract

This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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Other

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16 pages, 1102 KiB

Open AccessCase Report

Exploring Perforated Jejunal GIST: A Rare Case Report and Review of Molecular and Clinical Literature

by Milos Mirovic, Milica Dimitrijevic Stojanovic, Marina Jovanovic, Vesna Stankovic, Danijela Milosev, Natasa Zdravkovic, Bojan Milosevic, Aleksandar Cvetkovic, Marko Spasic, Berislav Vekic, Ivan Jovanovic, Bojana S. Stojanovic, Marko Petrovic, Ana Bogut, Miodrag Peulic and Bojan Stojanovic

Curr. Issues Mol. Biol. 2024, 46(2), 1192-1207; https://doi.org/10.3390/cimb46020076 - 1 Feb 2024

Cited by 1 | Viewed by 1531

Abstract

This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient’s postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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8 pages, 1561 KiB

Open AccessCase Report

Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report

by Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Liudmila V. Spirina and Alexander M. Volkov

Curr. Issues Mol. Biol. 2023, 45(9), 7642-7649; https://doi.org/10.3390/cimb45090481 - 19 Sep 2023

Cited by 1 | Viewed by 1310

Abstract

Introduction: The landscape of gastric cancer treatment has changed owing to the widespread use of immune checkpoint inhibitors. Autophagy, involved in regulating the immune system, is a potential trigger of immunity in tumors. This study aims to find molecular-based evidence for the effectiveness of FLOT chemotherapy with immune checkpoint inhibitors in gastric cancer patients. Materials and Methods: Three patients with advanced gastric cancer received FLOT neoadjuvant chemotherapy with immunotherapy and surgery. IHC was used to determine the PD-L1 status. Real-time PCR was used to analyze expression patterns of transcriptional growth factors, AKT/mTOR signaling components, PD-1, PD-L1, PD-L2 and LC3B. The LC3B content was measured via Western blotting analysis. Results: The combination of FLOT neoadjuvant chemotherapy and immunotherapy was found to be efficient in patients with a PD-L1-positive status. Gastric tumors with a PD-L1-positive status exhibited autophagy activation and decreased PD-1 expression. Conclusions: FLOT chemotherapy combined with immune checkpoint inhibitors showed high efficacy in gastric cancer patients with a positive PD-L1 status. Autophagy was involved in activating the tumor immunity. Further research is needed to clarify the mechanism of effective anticancer treatment. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

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