image: Figure 1: Mechanisms of Gastrointestinal Toxicity from Targeted Cancer Therapies. This schematic illustrates the major mechanistic pathways by which targeted therapies cause gastrointestinal toxicity. TKIs primarily act through vascular compromise, ADCs through direct epithelial injury, and CAR-T cells via cytokine-mediated inflammation. Other classes, including mTOR and PARP inhibitors, contribute apoptotic and DNA-repair–linked injury patterns. Abbreviations: ADC: Antibody–Drug Conjugate; CAR-T: Chimeric Antigen Receptor T-cell; CLDN18.2: Claudin 18.2; CRS: Cytokine Release Syndrome; GI: Gastrointestinal; mTOR: Mammalian Target of Rapamycin; PARP: Poly (ADP-ribose) Polymerase; TKI: Tyrosine Kinase Inhibitor; VEGF/VEGFR: Vascular Endothelial Growth Factor/(Receptor).
Credit: Copyright: © 2026 Hashim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“This review comprehensively examines the mechanisms, clinicopathological features, and management strategies of GI toxicity induced by TKIs, ADCs, and CAR-T therapies, emphasizing the diagnostic role of pathologists in identifying treatment-related injury patterns.”
BUFFALO, NY — February 20, 2026 — A new paper was published in Volume 13 of Oncoscience on February 6, 2026, titled “Gastrointestinal toxicity of targeted cancer therapies in the United States: Clinicopathologic patterns, FDA safety frameworks, and implications for national patient protection.”
First author Muhammad Moseeb Ali Hashim and co-corresponding author Kamran Zahoor from the University of Missouri-Columbia examined how targeted cancer therapies, including tyrosine kinase inhibitors, antibody–drug conjugates, and CAR-T cell therapies, affect the gastrointestinal tract. The authors analyzed clinical trials, FDA drug labels, national safety databases, and pathology reports. Their findings show that these therapies can cause distinct and sometimes serious digestive injuries that are often underrecognized. Greater awareness may support earlier diagnosis, better treatment decisions, and improved patient protection.
Targeted therapies have transformed care for colorectal cancer, gastric cancer, liver cancer, and gastrointestinal stromal tumors. By focusing on specific molecular targets, these drugs offer more precise treatment than traditional chemotherapy. However, they can also harm healthy tissue in the digestive system, making gastrointestinal toxicity an important clinical concern as their use expands.
The authors outline how different drug classes produce different patterns of injury. Tyrosine kinase inhibitors may reduce blood vessel growth in the gut, leading to diarrhea, abdominal pain, bleeding, or, in rare cases, bowel perforation. Antibody–drug conjugates can damage normal intestinal lining cells, causing nausea, vomiting, mouth sores, and colitis. CAR-T cell therapy may trigger widespread immune-related inflammation that also affects the gastrointestinal tract.
These side effects can resemble infections, inflammatory bowel disease, or reduced blood flow to the intestine. Biopsy samples may show cell death, ulceration, or inflammation, which can be misinterpreted without a clear treatment history. The authors highlight the importance of close collaboration between oncologists, gastroenterologists, and pathologists to ensure accurate diagnosis.
The paper also discusses national safety monitoring systems such as the FDA Adverse Event Reporting System, which tracks reported gastrointestinal complications linked to these therapies. Combining clinical findings with pathology data and regulatory safety information can strengthen drug monitoring and enhance patient safety nationwide.
“Looking forward, progress will depend on bridging critical research gaps particularly in real-world histopathology correlation, microbiome interactions, and predictive biomarkers of toxicity while embedding digital tools for patient-reported outcomes and pharmacovigilance.”
By integrating clinical, pathological, and regulatory perspectives, this research offers a practical framework for recognizing and managing gastrointestinal toxicity associated with targeted cancer therapies. As precision oncology advances, coordinated care and informed monitoring will remain essential to keep these treatments both effective and safe.
DOI: https://doi.org/10.18632/oncoscience.643
Correspondence to: Muhammad Moseeb Ali Hashim – mhdxz@umsystem.edu; Kamran Zahoor – kzwyc@health.missouri.edu
Abstract video: https://www.youtube.com/watch?v=HEd-pnk7aUg
Keywords: cancer, gastrointestinal toxicity, tyrosine kinase inhibitors, antibody-drug conjugates, CAR-T cell therapy, targeted cancer therapy
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Oncoscience is a peer-reviewed, open-access, traditional journal covering the rapidly growing field of cancer research, especially emergent topics not currently covered by other journals. This journal has a special mission: freeing oncology from publication costs. It is free to readers and authors.
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Journal
Oncoscience
Method of Research
News article
Subject of Research
Not applicable
Article Title
Gastrointestinal toxicity of targeted cancer therapies in the United States: Clinicopathologic patterns, FDA safety frameworks, and implications for national patient protection
Article Publication Date
6-Feb-2026
COI Statement
Authors have no conflicts of interest to declare.