Evidence map›Paper›PMID 40170495›Full record

ArticleClinical pharmacology and therapeutics2025

Identification and Clinical Evaluation of Potential Biomarkers for Breast Cancer Resistance Protein (BCRP/ABCG2).

Andrew M Riselli, Sook Wah Yee, Jia Yang, Claire M Brett, Kelsey Trumbach, Xujia Zhou, Renmeng Liu, Xiaomin Liang, Yurong Lai, Runlan Huo and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Andrew M RiselliDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-0714-5726
Sook Wah YeeDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-8121-8746
Jia YangDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-3992-4070
Claire M BrettDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Kelsey TrumbachDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Xujia ZhouDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0003-2491-0933
Renmeng LiuDrug Metabolism, Gilead Sciences Inc., Foster City, California, USA.
Xiaomin LiangDrug Metabolism, Gilead Sciences Inc., Foster City, California, USA.ORCID 0000-0002-8167-4634
Yurong LaiDrug Metabolism, Gilead Sciences Inc., Foster City, California, USA.ORCID 0000-0001-9505-333X
Runlan HuoDrug Metabolism and Pharmacokinetics, Bristol Myers Squibb, Princeton, New Jersey, USA.
Yongjun XueDrug Metabolism and Pharmacokinetics, Bristol Myers Squibb, Princeton, New Jersey, USA.
Hong ShenDrug Metabolism and Pharmacokinetics, Bristol Myers Squibb, Princeton, New Jersey, USA.
Lei ZhangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-0639-3162
Xinning YangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-8689-8231
Qi LiuOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-4053-4213
Shiew-Mei HuangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0003-1354-1394
Kathleen M GiacominiDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-8041-5430

Funding

FDA HHS U01 FD005978
6 · The paper itself

Abstract

Clinical inhibition and genetic variation of the Breast Cancer Resistance Protein (BCRP/ABCG2) efflux transporter can significantly influence drug exposure, highlighting the need for reliable BCRP functional biomarkers. This study aimed to identify and evaluate biomarkers predictive of BCRP function in humans. A comprehensive analysis of metabolomic genome-wide association studies (mGWAS) was conducted to discover potential BCRP biomarkers, followed by evaluation in in vitro transporter assays and a clinical drug-drug interaction (DDI) study. Across multiple mGWAS datasets, plasma concentrations of three herbicide derivatives-4-hydroxychlorothalonil (4HC), 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (BCDBA), and 3,5-dichloro-2,6-dihydroxybenzoic acid (DCDBA)-were significantly elevated (P < 5E-8) in individuals carrying reduced function ABCG2 polymorphisms. These compounds were confirmed as novel BCRP substrates via transporter uptake assays and selected for clinical evaluation alongside riboflavin, a known BCRP substrate and potential BCRP biomarker. In a DDI study with 11 healthy subjects, eltrombopag, a BCRP inhibitor, increased rosuvastatin concentrations by approximately twofold (P = 0.002). No significant changes in the plasma concentrations of organic anion transporting polypeptide 1B (OATP1B) biomarkers (CP-I and CP-III) or potential BCRP biomarkers (4HC, BCDBA, DCDBA, or riboflavin) were observed. Notably, two subjects were heterozygous carriers for the ABCG2 p.Q141K variant and exhibited significantly higher baseline concentrations of 4HC (P = 0.004) and BCDBA (P = 0.0003), consistent with reduced BCRP function. These findings suggest that 4HC and BCDBA are promising biomarkers for baseline BCRP function in specific populations, such as those harboring reduced function genetic polymorphisms, but do not appear suitable for detecting acute BCRP inhibition.

Indexed as

ATP Binding Cassette Transporter, Subfamily G, Member 2Neoplasm ProteinsAdultBiomarkersDrug InteractionsFemaleGenome-Wide Association StudyHumansMiddle AgedPolymorphism, Single NucleotideRosuvastatin CalciumABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2BiomarkersNeoplasm ProteinsRosuvastatin Calcium

Identifiers

PMID40170495
PMCPMC12166265

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.