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It reviews mechanistic evidence for telmisartan in esophageal squamous cell carcinoma via signaling inhibition and microRNA changes, and discusses microRNAs in therapy response and radioresistance. It also considers GLP1 agonists and metabolic pathways for hepatocellular carcinoma 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Masuzaki , Reina Sasaki-Tanaka , Hirofumi Kogure  and Mitsuhiko Moriyama   \nCitation: Kanda, T.; Masuzaki, R.; Sasaki-Tanaka, R.; Kogure, H.; Moriyama, M. Molecular Mechanisms, Diagnosis and Treatments in Digestive Malignancy. Int. J. Mol. Sci. 2023, 24, 6471 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24076471  \nReceived: 22 March 2023  \nAccepted: 28 March 2023  \nPublished: 30 March 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDivision of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; [masuzaki.ryota@nihon-u.ac.jp](masuzaki.ryota@nihon-u.ac.jp) (R.M.);  \n[moriyama.mitsuhiko@nihon-u.ac.jp](moriyama.mitsuhiko@nihon-u.ac.jp) (M.M.)  \n* Correspondence: [kanda.tatsuo@nihon-u.ac.jp](kanda.tatsuo@nihon-u.ac.jp); Tel.: +81-3-3972-8111  \nKeywords: transient receptor potential channel; microRNAs; telmisartan; glucagon-like peptide 1 agonist; HCC; innate immune response  \nIn this Special Issue,“Molecular Mechanisms, Diagnosis and Treatments in Digestive Malignancy”, of the International Journal of Molecular Sciences, a total of 10 impactful articles have been published.  \nStokłosa et al. reviewed the transient receptor potential (TRP) channel family, among ion channels, finding that it plays a role in digestive tract cancers [1] . The member of the TRP channel family have been classified into six human TRP channel subfamilies, including canonical (TRPC), melastatin (TRPM), vanilloid (TRPV), ankyrin (TRPA), polycystic (TRPP), and mucolipin (TRPML) channels. Most TRP channels play an essential role in the influx of monovalent and divalent cations, such as Na+, Mg2+, and Ca2+, as well as trace metal ions. Mutations in the TRP genes are not involved in most of the TRP channels' changes in cancer. Increased or decreased levels of the expression of functional TRP proteins are involved depending on the cancer's stage. The different expression patterns of TRP channels were observed inhuman oral cancer, esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma (HCC), pancreatic cancer, and gastric and colorectal cancers. It is possible that the TRP channels may be potential cancer biomarkers or therapeutic targets [1,2] .  \nTelmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), inhibits the proliferation of human ESCC in vitro and in vivo [3] . Telmisartan inhibits the phosphorylation of ErbB3, a member of the epidermal growth factor receptor (EGFR) family, and inhibits cell-cycle progression from synthesis (S) to the gap 2 (G2)/mitosis and cytokinesis (M) phase by decreasing the expression of cyclin A2 and cyclin-dependent kinase 2 (Cdk2) inhuman ESCC KYSE180 cells [3] . Telmisartan also decreases the thrombospondin-1 levels in KYSE180 cells [3] . A total of 36 and 23 MicroRNAs (miRNAs) were upregulated and downregulated, respectively, in KYSE180 cells treated with telmisartan [3] . The growth of KYSE180 tumors in nude mice was inhibited by the treatment of telmisartan [3] . Telmisartan may be effective for ESCC.  \nMany patients with esophageal adenocarcinoma do not benefit from chemoradiotherapy treatment due to therapy resistance [4] . miRNAs, small (19–24 nucleotides) non-coding RNA molecules, in small extracellular vesicles, comprise a stable form of circulating nucleic acids that are useful for diagnosis and as biomarkers that are predictive of treatment response [5] . Butz et al. demonstrated that the inhibition of miR-451a enhances radiosensitivity in ","cbCairersMs51Lu0","https://ap.wps.com/l/cbCairersMs51Lu0","pdf",196349,"English","# Editorial\n## TRP channels in digestive tract cancers\n## Telmisartan and microRNA-mediated mechanisms in ESCC\n## MicroRNAs as diagnostic biomarkers and treatment response predictors\n## GLP1 agonists and metabolic regulation in HCC","[{\"question\":\"What do TRP channels contribute to in digestive tract cancers?\",\"answer\":\"TRP channels are implicated in the influx of cations and show altered expression patterns across several digestive cancers, supporting their potential as biomarkers or therapeutic targets.\"},{\"question\":\"How does telmisartan affect esophageal squamous cell carcinoma in the studies cited?\",\"answer\":\"Telmisartan inhibits proliferation by affecting signaling such as ErbB3 phosphorylation, disrupts cell-cycle progression, reduces thrombospondin-1 levels, and alters microRNA expression profiles in treated cells and tumor models.\"},{\"question\":\"Why are microRNAs emphasized for diagnosis and treatment response in digestive malignancy?\",\"answer\":\"MicroRNAs in small extracellular vesicles provide stable circulating nucleic acids, enabling diagnosis and prediction of treatment response, including links to radiosensitivity and resistance patterns.\"}]","Molecular Mechanisms, Diagnosis and Treatments in Digestive Malignancy - Editorial | PDF",1790226941]