Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response
This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.
About the trial
The metabolism of anticancer drugs is influenced by genetic variants that affect their bioavailability and toxicity. In the case of antibody-drug conjugates (ADCs), such as sacituzumab-govitecan (SG), trastuzumab-deruxtecan (T-DXd), and datopotamab-deruxtecan (Dato-DXd), the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a central role in the glucuronidation and elimination of their cytotoxic components. In particular, the metabolism of SN-38, the active metabolite of irinotecan and SG, is highly influenced by variants in UGT1A1, leading to drug accumulation and the development of severe toxicities. Patients with variants such as UGT1A1\*28 (rs3064744) and UGT1A1\*6 (rs4148323) exhibit reduced enzyme activity, increasing the risk of neutropenia and severe diarrhea. The relevance of UGT1A1 is not limited to sacituzumab-govitecan; its role in the elimination of camptothecin derivatives suggests it could also impact the toxicity of trastuzumab-deruxtecan and datopotamab-deruxtecan, which contain deruxtecan, a cytotoxic agent 10 times more potent than irinotecan. Despite strong evidence linking the UGT1A1 genotype to irinotecan toxicity, there are currently no established pharmacogenetic recommendations for antidiuretic peptides (ADCs) in metastatic breast cancer.
Original English text from ClinicalTrials.gov
Who can (and can't) join
✓ Qualifies
- •Wiek 18 lat lub więcej
- •Diagnoza raka piersi i rozpoczęcie lub trwająca terapia jednym z leków: Sacituzumab Govitecan, Trastuzumab Deruxtecan lub Datopotamab Deruxtecan
- •Podpisana zgoda na uczestnictwo w badaniu genetycznym
✗ Disqualifies
- •Pacjenci, którzy ostatecznie nie będą leczeni wymienionymi lekami
- •Odmowa wyrażenia zgody na analizę genetyczną
Simplified criteria — AI translation
Trial details
- Minimum age
- 18 Years
- Last updated (source)
- May 13, 2026
- Sex
- No restrictions
Therapies / drugs in trial
Locations (1)
Hospital Universitario Clínico San Cecilio
Granada, Spain
Trial contact
Isabel Blancas López-Barajas, MD, PhD
Contact information from ClinicalTrials.gov. Contact in English.
Data from ClinicalTrials.gov. AI-assisted translation, last sync: 7/1/2026.