DNA strand intertwined with chemotherapy pills and cancer cell fading

Irinotecan Toxicity: Can Your Genes Predict Your Reaction?

Avery Sinclair in Health & Wellness December 2025 • 4 min read.

"New research explores how genetic variations can influence the effectiveness and side effects of irinotecan, a key chemotherapy drug for metastatic colorectal cancer."

Irinotecan (CPT-11) is a chemotherapy drug commonly used to treat metastatic colorectal cancer (mCRC). It works by converting into an active form called SN-38, which stops cancer cells from replicating their DNA. However, after SN-38 does its job, the body needs to get rid of it through a process called glucuronidation, which is handled by liver enzymes. If these enzymes don't work correctly due to genetic variations, SN-38 can build up in the body and cause severe side effects like diarrhea and neutropenia (low white blood cell count).

One of the most well-known genetic variations affecting irinotecan's toxicity is UGT1A128. This variation reduces the activity of the liver enzyme responsible for clearing SN-38, leading to higher levels of the drug in the blood and increased risk of side effects. Other genetic variations in the UGT1A family, like UGT1A160, UGT1A7, and UGT1A9, may also play a role, but their effects are still being studied.

Beyond glucuronidation, other proteins in the body, such as ABC transporters and SLC transporters, also influence how irinotecan is processed and whether it causes toxicity. These transporters help move the drug in and out of cells, affecting its concentration in different parts of the body. Variations in the genes that control these transporters, like ABCB1, ABCC2, and SLCO1B1, have been linked to differences in how people respond to irinotecan treatment.

How Do Genetic Variations Affect Irinotecan Toxicity?

DNA strand intertwined with chemotherapy pills and cancer cell fading

A recent study published in Medicina Clinica investigated the connection between genetic variations in UGT, SLCO, ABCB, and ABCC genes and the risk of toxicity in patients with mCRC treated with irinotecan. The researchers aimed to see if they could predict which patients were more likely to experience side effects based on their genetic makeup.

The study involved 34 patients with mCRC who were treated with the FOLFIRI regimen (a combination of irinotecan, fluorouracil, and leucovorin). The researchers collected blood samples from the patients and analyzed their DNA to identify variations in the UGT1A1, UGT1A7, UGT1A9, ABCB1, ABCC2, and SLCO1B1 genes. They then tracked the patients' side effects during treatment and looked for correlations between specific genetic variations and the occurrence of toxicity.

The study found that certain genetic variations, including rs8175347, rs17868323, rs3832043, rs11692021, and rs7577677, were linked to a higher risk of adverse effects.
Patients with the wild-type (normal) version of UGT family genes had lower rates of toxicity compared to those with mutated versions.
Specific mutated alleles in rs17868323 and rs3832043 were associated with increased gastrointestinal toxicity.
The presence of any mutated allele in the UGT1A gene family was related to a higher incidence of irinotecan-induced toxicity.

These findings suggest that genetic testing for UGT1A gene variations could help identify patients who are at higher risk of experiencing side effects from irinotecan treatment. By knowing a patient's genetic profile, doctors may be able to adjust the dose of irinotecan or choose a different treatment option to minimize toxicity and improve outcomes.

The Future of Personalized Cancer Treatment

The study adds to the growing body of evidence that genetic variations play a significant role in how people respond to cancer treatment. As we learn more about the complex interplay between genes and drugs, we can move closer to personalized medicine, where treatments are tailored to each individual's unique genetic makeup. This approach has the potential to improve the effectiveness of cancer treatment while reducing the risk of debilitating side effects, ensuring better outcomes and a higher quality of life for patients.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.medcle.2018.01.038, Alternate LINK

Title: Effect Of Ugt, Slco, Abcb And Abcc Polymorphisms On Irinotecan Toxicity

Subject: General Medicine

Journal: Medicina Clínica (English Edition)

Publisher: Elsevier BV

Authors: Sara García Gil, Ruth Ramos Díaz, Gloria Julia Nazco Casariego, Marta Llanos Muñoz, Maria Micaela Viña Romero, Braulio Martín Calero, Jose Antonio Pérez Pérez, Fernando Gutiérrez Nicolás

Published: 2018-12-01

Everything You Need To Know

What is irinotecan used for, and how does it work?

Irinotecan (CPT-11) is a chemotherapy drug primarily used to treat metastatic colorectal cancer (mCRC). It functions by converting into an active form called SN-38, which inhibits the replication of cancer cells' DNA. After SN-38 has done its job, the body removes it through glucuronidation, a process managed by liver enzymes.

How do specific genetic variations, like UGT1A1*28, impact the effectiveness and safety of irinotecan?

Genetic variations, such as UGT1A1*28, influence the activity of the liver enzyme responsible for clearing SN-38, the active form of irinotecan. For instance, UGT1A1*28 reduces this enzyme's activity. This leads to a buildup of SN-38 in the body, increasing the risk of severe side effects like diarrhea and neutropenia. Other variations within the UGT1A family (UGT1A1*60, UGT1A7, and UGT1A9) can also affect this process, although their exact roles are still under investigation.

Besides UGT genes, what other genetic factors are involved in irinotecan toxicity, and how?

Besides the UGT genes, ABC transporters and SLC transporters also affect irinotecan toxicity. These transporters influence how irinotecan is processed and whether it causes toxicity. Variations in the genes that control these transporters, such as ABCB1, ABCC2, and SLCO1B1, have been linked to differences in how people respond to irinotecan treatment. They affect the movement of the drug in and out of cells, thereby influencing its concentration in different parts of the body.

How can genetic testing contribute to improving outcomes for patients undergoing irinotecan treatment?

Genetic testing for variations in the UGT1A gene family can help identify patients at higher risk of irinotecan-related side effects. By understanding a patient's genetic profile, doctors can adjust the irinotecan dosage or select alternative treatments, minimizing toxicity. This personalized approach could lead to improved treatment outcomes, reduce debilitating side effects, and enhance the quality of life for cancer patients.

What are the implications of using personalized medicine in cancer treatment, and how does this apply to irinotecan therapy?

Personalized medicine involves tailoring treatments based on an individual's unique genetic makeup. In the context of irinotecan, this means considering genetic variations in genes like UGT, SLCO, ABCB, and ABCC. By understanding these variations, healthcare providers can predict a patient's response to the drug, potentially adjusting the dose or choosing alternative treatments to improve effectiveness and minimize toxicity. This approach promises to improve cancer treatment effectiveness while reducing side effects, leading to better patient outcomes and quality of life.