Toxic side effects of targeted therapies for GI cancers may be under recognized

Image representing gastrointestinal damage – AI created by WIX

CANCER DIGEST – Feb. 22, 2026 – Targeted therapies that have pushed significantly higher survival rates for colorectal cancer, gastric cancer, liver cancer, and gastrointestinal stromal tumors, may have unrecognized long-term toxic side effects, according to an international group of researchers.

The findings published in the Feb. 6, 2026, journal Oncoscience resulted from a massive data analysis led by Muhammad Moseeb Ali Hashim, of the Department of Pathology and Laboratory Sciences, University of Missouri-Columbia.

The researchers analyzed data from FDA drug labeling, the FDA’s post-marketing surveillance of adverse effects reporting (FAERS) database, and pivotal clinical trials for three classes of targeted therapies.

These include TKIs or tyrosine kinase inhibitors, which attack tumors by blocking the tumor’s ability to grow blood vessels needed for growth, ADCs or antibody-drug combinations that use antibodies to carry anti-cancer agents directly into tumors, and CAR-T Therapies that use anti-tumor immune cells taken from a patient, grown into huge numbers and reinfused into the patients to overwhelm the cancer.

What the researchers found from their data analysis was that while these therapies have been highly effective in anti-cancer action, they can also cause specific types of injury to different areas of gastrointestinal tract that have been underrecognized as toxicities of the therapies.

The authors found that each drug class produces 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.

The researchers found that unlike traditional chemotherapy, the GI toxicities associated with targeted therapies are often idiosyncratic (individualized), variable in onset and severity, and the mechanism of action can be distinct for each drug class.

As a result, the recognition of symptoms as side effects of the treatment as opposed to standard infections or unrelated inflammation of the colon is a challenge to pathologists for making the correct diagnosis.

As these therapies become the standard of care, more people will be treated with one or more of these therapies. As a result, the researchers called for greater multidisciplinary management and more pathologic monitoring to develop a clearer picture of the extent of the side effects of these therapies to ensure that the “cure” does not carry undue cost to patients’ quality of life. 

Sources: Eurekalert press release and the journal Oncoscience