Novel Strategies in the Prevention/Treatment of Colorectal Cancer

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2675

Special Issue Editors


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Guest Editor
Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Interests: fluoropyrimidine; colorectal cancer; thymidylate synthase; DNA topoisomerase 1; DNA repair
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Guest Editor
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA
Interests: colon and rectal cancer; drug discovery; experimental therapeutics

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Guest Editor
Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Interests: colorectal cancer; colitis-associated CRC; cancer prevention

Special Issue Information

Dear Colleagues,

The signaling pathways dysregulated during canonical CRC initiation and progression are potential targets for both chemoprevention and cancer treatment. However, the Wnt, P53, and TGF-b pathways have not been fully exploited for drug development to either reduce CRC incidence or improve treatment, in part because of their key role in normal tissue homeostasis and the difficulty in developing drugs for these targets. Chemoprevention of CRC for high-risk individuals (e.g., Lynch syndrome) is still under development, but with promising preclinical results targeting mediators of inflammation such as COX-2 and other targets such as HMG-CoA reductase. Cancer interception is a new strategy for which target pathway identification is in its infancy. In contrast, adjuvant chemotherapy for locally advanced CRC uses fluoropyrimidine combinations such as FOLFOX to target TS and DNA damage, while treatment of metastatic disease may use these same combinations of drugs or antibodies targeting EGFR, VEGF, and more recently BRAF and KRAS, but innovative strategies continue to be developed to personalize the therapeutic approach.

The current Special Issue will focus on original research articles and comprehensive reviews illuminating the most recent advances in understanding molecular pathways of CRC initiation and progression that are amenable to therapeutic intervention. Studies identifying and validating novel pathways or targets for preventing or treating CRC are of special interest; however, innovative approaches for well-validated targets for CRC therapy including TS, DNA topoisomerase 1, EGFR, and other targets are also of interest. Innovative approaches to use chemotherapy in combination with immunotherapy and for the development of cancer vaccines are of special interest.

Prof. Dr. William H. Gmeiner
Prof. Dr. Dan A. Dixon
Prof. Dr. Margie Lee Clapper
Guest Editors

Manuscript Submission Information

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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

  • colorectal cancer
  • chemotherapy
  • chemoprevention
  • targeted therapy
  • kinase inhibitor
  • immunotherapy

Published Papers (2 papers)

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Research

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15 pages, 6654 KiB  
Article
TIM-3 Expression and M2 Polarization of Macrophages in the TGFβ-Activated Tumor Microenvironment in Colorectal Cancer
by Masanori Katagata, Hirokazu Okayama, Shotaro Nakajima, Katsuharu Saito, Takahiro Sato, Mei Sakuma, Satoshi Fukai, Eisei Endo, Wataru Sakamoto, Motonobu Saito, Zenichiro Saze, Tomoyuki Momma, Kosaku Mimura and Koji Kono
Cancers 2023, 15(20), 4943; https://doi.org/10.3390/cancers15204943 - 11 Oct 2023
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Abstract
TGFβ signaling in the tumor microenvironment (TME) drives immune evasion and is a negative predictor of immune checkpoint inhibitor (ICI) efficacy in colorectal cancer (CRC). TIM-3, an inhibitory receptor implicated in anti-tumor immune responses and ICI resistance, has emerged as an immunotherapeutic target. [...] Read more.
TGFβ signaling in the tumor microenvironment (TME) drives immune evasion and is a negative predictor of immune checkpoint inhibitor (ICI) efficacy in colorectal cancer (CRC). TIM-3, an inhibitory receptor implicated in anti-tumor immune responses and ICI resistance, has emerged as an immunotherapeutic target. This study investigated TIM-3, M2 macrophages and the TGFβ-activated TME, in association with microsatellite instability (MSI) status and consensus molecular subtypes (CMSs). Transcriptomic cohorts of CRC tissues, organoids and xenografts were examined (n = 2240). TIM-3 and a TGFβ-inducible stromal protein, VCAN, were evaluated in CRC specimens using immunohistochemistry (n = 45). TIM-3 expression on monocytes and generated M2 macrophages was examined by flow cytometry. We found that the expression of HAVCR2 (TIM-3) significantly correlated with the transcriptional signatures of TGFβ, TGFβ-dependent stromal activation and M2 macrophage, each of which were co-upregulated in CMS4, CMS1 and MSI CRCs across all datasets. Tumor-infiltrating TIM-3+ immune cells accumulated in TGFβ-responsive cancer stroma. TIM-3 was increased on M2-polarized macrophages, and on monocytes in response to TGFβ treatment. In conclusion, we identified a close association between TIM-3 and M2-like polarization of macrophages in the TGFβ-rich TME. Our findings provide new insights into personalized immunotherapeutic strategies based on the TME for CRCs. Full article
(This article belongs to the Special Issue Novel Strategies in the Prevention/Treatment of Colorectal Cancer)
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Review

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19 pages, 1200 KiB  
Review
Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment
by William H. Gmeiner
Cancers 2024, 16(5), 1029; https://doi.org/10.3390/cancers16051029 - 02 Mar 2024
Cited by 1 | Viewed by 1139
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC mortality results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy is often a preferred therapeutic option. Biomarker-based stratification of mCRC enables the use of precision therapy based on individual [...] Read more.
Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC mortality results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy is often a preferred therapeutic option. Biomarker-based stratification of mCRC enables the use of precision therapy based on individual tumor mutational profiles. Activating mutations in the RAS/RAF/MAPK pathway downstream of EGFR signaling have, until recently, limited the use of EGFR-targeted therapies for mCRC; however, the development of anti-RAS and anti-RAF therapies together with improved strategies to limit compensatory signaling pathways is resulting in improved survival rates in several highly lethal mCRC sub-types (e.g., BRAF-mutant). The use of fluoropyrimidine (FP)-based chemotherapy regimens to treat mCRC continues to evolve contributing to improved long-term survival. Future advances in chemotherapy for mCRC will need to position development relative to the advances made in precision oncology. Full article
(This article belongs to the Special Issue Novel Strategies in the Prevention/Treatment of Colorectal Cancer)
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