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BIOMARKER:

UGT1A1*28

i
Other names: UGT1A1, UDP glucuronosyltransferase family 1 member A1, GNT1, UGT1, UDPGT, UGT1A, HUG-BR1, BILIQTL1, UDPGT 1-1
Entrez ID:
Related biomarkers:
16d
Clinical Benefits and Utility of Pretherapeutic DPYD and UGT1A1 Testing in Gastrointestinal Cancer: A Secondary Analysis of the PREPARE Randomized Clinical Trial. (PubMed, JAMA Netw Open)
To date, the clinical benefit and utility of implementing a DPYD/UGT1A1 pharmacogenetic-informed therapy with fluoropyrimidines and/or irinotecan have not been prospectively investigated...Clinical benefit did not appear to be affected. ClinicalTrials.gov Identifier: NCT03093818.
Clinical • Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • DPYD (Dihydropyrimidine Dehydrogenase)
|
UGT1A1*28 • UGT1A1*1*1
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irinotecan
22d
Pharmacogenetic-guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC-PGx): A multicenter clinical trial. (PubMed, Clin Transl Sci)
PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings.
Clinical • Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • DPYD (Dihydropyrimidine Dehydrogenase)
|
UGT1A1*28 • UGT1A1*1*1
|
irinotecan
1m
Liposomal Irinotecan Based FOLFIRI With Bevacizumab in First-line Treatment of Advanced Colorectal Cancer (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Fudan University | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Jul 2025
Enrollment closed • Trial primary completion date • Metastases
|
BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
BRAF mutation • RAS mutation • UGT1A1*28 • UGT1A1*1*1
|
Avastin (bevacizumab) • 5-fluorouracil • leucovorin calcium
1m
Efficacy and safety of sacituzumab govitecan Trop-2-targeted antibody-drug conjugate in solid tumors and UGT1A1*28 polymorphism: a systematic review and meta-analysis. (PubMed, BJC Rep)
Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data.
Retrospective data • Review • Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Trodelvy (sacituzumab govitecan-hziy)
2ms
Enrollment open • Combination therapy
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
temozolomide • vincristine • locnartecan (PEN-866)
3ms
Neoadjuvant sacituzumab govitecan, followed by radical cystectomy, for patients with muscle-invasive bladder cancer (MIBC): Updated interim results of SURE-01 trial (ESMO Asia 2024)
Methods Pts with cT2-4N0M0 MIBC with pure/predominant urothelial carcinoma histology, who were ineligible for or refused cisplatin-based chemotherapy, received 4 cycles of SG 10 mg/kg (days 1,8 q3w) followed by RC. Conclusions The observed ypT0N0-x responses after neoadjuvant SG demonstrate promising activity in MIBC, unveiling a potential to avoid RC. Reduced dose of SG was feasible, and the data support the ongoing SURE-01 study in MIBC.
Clinical
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Signatera™
|
cisplatin • Trodelvy (sacituzumab govitecan-hziy)
8ms
New P2 trial
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1 • UGT1A1*28 + UGT1A1*6
|
cisplatin • etoposide IV • Beleodaq (belinostat)
8ms
Irinotecan dosing and pharmacogenomics: a comprehensive exploration based on UGT1A1 variants and emerging insights. (PubMed, J Chemother)
Hence, screening for UGT1A1 polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on UGT1A1*28 and UGT1A1*6 variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of UGT1A1 genotype testing.
Review • Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1 • UGT1A1*28 + UGT1A1*6
|
irinotecan
9ms
Individual Irinotecan Therapy Under the Guidance of Pre-Treated UGT1A1*6 Genotyping in Gastric Cancer. (PubMed, Technol Cancer Res Treat)
One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.
Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
paclitaxel • irinotecan
9ms
Diversity of oncopharmacogenetic profile within Spanish population. (PubMed, Pharmacogenet Genomics)
The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.
Journal
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • DPYD (Dihydropyrimidine Dehydrogenase)
|
UGT1A1*28 • UGT1A1*1*1
|
irinotecan
12ms
UGT1A1 genotype-guided irinotecan dosing during neoadjuvant chemoradiotherapy for locally advanced rectal cancer: A prospective analysis of SN-38 concentration. (PubMed, Int J Cancer)
All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m ; UGT1A1*1*28: 65 mg/m ) and capecitabine (CapIri). We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.
Journal • Metastases
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
capecitabine • irinotecan
12ms
Trial completion date • Trial primary completion date • Circulating tumor DNA • Metastases
|
BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Signatera™
12ms
Trial completion date • Combination therapy
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
5-fluorouracil • oxaliplatin • leucovorin calcium • Onivyde (nanoliposomal irinotecan)
1year
RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
P2, N=78, Recruiting, Canadian Cancer Trials Group
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
|
Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
1year
Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer (clinicaltrials.gov)
P1, N=24, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Dec 2023
Enrollment open • Trial initiation date
|
KRAS (KRAS proto-oncogene GTPase) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
KRAS mutation • KRAS G12C • KRAS G12 • UGT1A1*28 • UGT1A1*1*1
|
Erbitux (cetuximab) • irinotecan • Krazati (adagrasib)
1year
Genetic variations underlying Gilbert syndrome and HBV infection outcomes: a cross-sectional study. (PubMed, Front Genet)
We showed that the accumulation of UGT1A1 variants or the rarity of the variation is associated with a better prognosis, and the effect magnitude correlates with UGT1A1 deficiency. This study demonstrates the therapeutic potential of host UGT1A1 variations underlying GS against HBV infection outcomes.
Observational data • Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1 • UGT1A1 mutation • UGT1A1 wild-type
1year
Enrollment change • Enrollment closed • Circulating tumor DNA • Metastases
|
BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Signatera™
over1year
Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer (clinicaltrials.gov)
P1, N=24, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Jul 2023 --> Jul 2024
Trial initiation date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
KRAS mutation • KRAS G12C • KRAS G12 • UGT1A1*28 • UGT1A1*1*1
|
Erbitux (cetuximab) • irinotecan • Krazati (adagrasib)
over1year
New P2 trial • Surgery
|
BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
BRAF mutation • RAS mutation • UGT1A1*28 • UGT1A1*1*1 • UGT1A1 mutation
|
5-fluorouracil • oxaliplatin • irinotecan • Fruzaqla (fruquintinib) • leucovorin calcium
over1year
Trial primary completion date • Combination therapy
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
5-fluorouracil • oxaliplatin • leucovorin calcium • Onivyde (nanoliposomal irinotecan)
over1year
New P2 trial • Metastases
|
BRAF (B-raf proto-oncogene) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
BRAF mutation • RAS mutation • UGT1A1*28 • UGT1A1*1*1 • UGT1A1 mutation
|
Avastin (bevacizumab) • 5-fluorouracil • leucovorin calcium
over1year
Irinotecan Toxicity With UGT1A Polymorphism in a Patient With Metastatic Rectal Adenocarcinoma (ACG 2023)
Most recently he received treatment with FOLFIRI and Cetuximab, with a FUDR hepatic arterial infusion pump...Broad spectrum antibiotics, scheduled diphenoxylate and loperamide were initiated with no improvement...Bowel movements improved with intravenous steroids which were transitioned to oral prednisone outpatient...Our case emphasizes standardized pre-therapeutic UGT1A1 testing due to the increased morbidity and mortality associated with IRI toxicity in these patients. It also highlights the need for closer monitoring for adverse drug events to reduce the overall healthcare burden and complications.
Clinical • Metastases
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KRAS (KRAS proto-oncogene GTPase) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
KRAS wild-type • RAS wild-type • UGT1A1*28 • UGT1A1*1*1
|
Erbitux (cetuximab) • 5-fluorouracil • irinotecan • prednisone • leucovorin calcium • loperamide
over1year
ASSOCIATION BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS AND NEUTROPENIA CAUSED BY TRIPLET CHEMOTHERAPY IN PATIENTS WITH PANCREATIC CANCER (UEGW 2023)
Moreover, 5-fluorouracil with leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) therapy has been shown to be effective as a triplet chemotherapy for poor prognostic pancreatic cancer, however, a high frequency of severe neutropenia is known. The combination of biomarker SNPs in the NFTC1 and SLC14A1 genes may be a useful predictor for the toxicity of triplet chemotherapy for pancreatic cancer.
Clinical
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • NFATC1 (Nuclear Factor Of Activated T Cells 1)
|
UGT1A1*28 • UGT1A1*1*1
|
5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
over1year
Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
P2, N=240, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting
Enrollment open
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
over1year
Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
P2, N=240, Not yet recruiting, German Cancer Research Center | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Apr 2029 --> Mar 2030
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
over1year
Predictive Value of ABCC2 and UGT1A1 Polymorphisms on Irinotecan-Related Toxicities in Patients with Cancer. (PubMed, Genet Test Mol Biomarkers)
Grades III/IV of nausea were more frequently associated with the ABCC2-1549 AA genotype (83.3% p = 0.004) in patients with colorectal cancer. In pancreatic cancer, a significant absence of diarrhea grades III-IV was noted in patients with the ABCC2 1249 GG genotype compared to the other ABCC2 1249 genotypes.
Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • ABCC2 (ATP Binding Cassette Subfamily C Member 2)
|
UGT1A1*28 • UGT1A1*1*1
|
irinotecan
over1year
RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
P2, N=78, Recruiting, Canadian Cancer Trials Group | Not yet recruiting --> Recruiting | Initiation date: Jan 2023 --> Apr 2023
Enrollment open • Trial initiation date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
|
Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
over1year
Characterization of Enzymes Involved in Nintedanib Metabolism in Humans. (PubMed, Drug Metab Dispos)
Significance Statement To our knowledge, this is the first study to characterize the enzymes responsible for each step of nintedanib metabolism in the human body. We found that β-glucuronidase may contribute to BIBF1202-G deglucuronidation.
Journal
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UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • UGT1A7 (UDP Glucuronosyltransferase Family 1 Member A7)
|
UGT1A1*28 • UGT1A1*1*1 • UGT1A1 wild-type
|
nintedanib
over1year
A Phase I Study of a Combination of Liposomal Irinotecan and Veliparib in Solid Tumors. (PubMed, Oncologist)
The clinical trial was terminated due to high frequency of unacceptable gastrointestinal toxicities, which precluded dose escalation of veliparib in combination with nal-IRI (ClinicalTrials.gov Identifier: NCT02631733).
P1 data • Clinical Trial,Phase I • Journal
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
veliparib (ABT-888) • Onivyde (nanoliposomal irinotecan)
over1year
UGT1A1 *28/*28 genotype and risk of toxicity and disease progression in breast cancer patients treated with sacituzumab govitecan-hziy. (ASCO 2023)
Despite the relatively small sample size, 25% of patients had the *28/*28 genotype. We confirmed that *28/*28 is associated with a higher risk for discontinuation of SG for toxicity without an association to disease progression based on mutation status. Early UGT1A1 testing as standard practice may identify patients at risk for excess toxicity, who may undergo early dose reductions to prevent discontinuation of this important advanced breast cancer treatment.
Clinical
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Trodelvy (sacituzumab govitecan-hziy)
over1year
Enrollment closed • Combination therapy
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
5-fluorouracil • oxaliplatin • leucovorin calcium • Onivyde (nanoliposomal irinotecan)
over1year
UGT1A1 Genotyping in Taiwanese Cancer Patients (clinicaltrials.gov)
P=N/A, N=100, Not yet recruiting, National Taiwan University Hospital
New trial
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
irinotecan
almost2years
Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
P2, N=240, Not yet recruiting, German Cancer Research Center | Initiation date: Dec 2022 --> May 2023
Trial initiation date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
almost2years
New P1 trial • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
KRAS mutation • KRAS G12C • KRAS G12 • UGT1A1*28 • UGT1A1*1*1
|
Erbitux (cetuximab) • irinotecan • Krazati (adagrasib)
almost2years
Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group. (PubMed, J Exp Clin Cancer Res)
Chemotherapy-related hyperbilirubinemia is a prognostic factor for treatment outcome in pediatric ALL and genetic variation in UGT1A aids in predicting the clinical impact of hyperbilirubinemia.
Journal
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
almost2years
Trial primary completion date • Combination therapy
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
5-fluorouracil • oxaliplatin • leucovorin calcium • Onivyde (nanoliposomal irinotecan)
2years
Association between ABCG2, ABCB1, ABCC2 efflux transporters SNP's and irinotecan adverse effects in colorectal cancer patients: a real life study. (PubMed, Clin Pharmacol Ther)
In a sensitivity analysis, adjusted for UGT1A1 status and for possible demographic and clinical confounders, adjusted OR was 0.56 [0.33, 0.94] for the association between rs2231142 (ABCG2) and the composite outcome. In conclusion, we describe novel association between the minor allele of rs2231142 in the efflux transporter gene ABCG2 and protection against severe side effects in CRC patients treating with irinotecan.
Journal • Adverse events
|
ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • ABCC2 (ATP Binding Cassette Subfamily C Member 2)
|
UGT1A1*28 • UGT1A1*1*1
|
irinotecan
2years
Prevalence of UGT1A1 polymorphisms in gastrointestinal cancer: A single-institutional retrospective study. (ASCO-GI 2023)
The prevalence of heterozygous and homozygous of UGT1A1*28 polymorphism in GI cancer patients in the Appalachian region is 51.5%, consistent with the reported literature. Homozygous and heterozygous UGT1A1 *28 alterations constituted 13.2 and 38.3% respectively. Data collection for pre-emptive chemotherapy dosage adjustments and adverse events is ongoing to integrate testing for UGT1A1 polymorphism routinely for all GI malignancies cancer patients starting irinotecan chemotherapy.
Retrospective data
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
irinotecan
2years
Enrollment open • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Signatera™
2years
RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
P2, N=78, Not yet recruiting, Canadian Cancer Trials Group
New P2 trial • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
|
Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
2years
Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity. (PubMed, Cancer Med)
Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.
Journal
|
UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium
2years
Trial suspension • Circulating tumor DNA
|
BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
UGT1A1*28 • UGT1A1*1*1
|
Signatera™