Evidence map›Paper›PMID 41449800›Full record

ArticleHGG advances2026

Understanding exceptional response: The role of MINDY1 SNP in CDK4/6 inhibitor therapy for ER

Eleni Balla, Yi Li, Zikun Zhou, John T Nguyen, Kyriaki Papadopoulou, Evangelia Razis, Angelos Koutras, Eleni Galani, Giannis Mountzios, Ourania Romanidou and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

18 authors.

Eleni BallaBioengineering Department, The University of Texas at Dallas, Richardson, TX, USA; Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA.
Yi LiBioengineering Department, The University of Texas at Dallas, Richardson, TX, USA; Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA.
Zikun ZhouBioengineering Department, The University of Texas at Dallas, Richardson, TX, USA; Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA.
John T NguyenBioengineering Department, The University of Texas at Dallas, Richardson, TX, USA; Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA.
Kyriaki PapadopoulouLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
Evangelia RazisThird Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
Angelos KoutrasDivision of Oncology, Department of Medicine, University Hospital of Patras, Medical School, Patras, Greece.
Eleni GalaniSecond Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
Giannis MountziosFourth Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece.
Ourania RomanidouDepartment of Medicine, Medical Oncology Unit, Giannitsa General Hospital, Giannitsa, Greece.
George FountzilasAristotle University of Thessaloniki, Thessaloniki, Greece.
Athina ChristopoulouMedical Oncology Unit, St. Andrew's Hospital, Patras, Greece.
Dimitris TryfonopoulosSecond Department of Internal Medicine, Agios Savvas Cancer Hospital, Athens, Greece.
Panagiota OikonomopoulouSection of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Zenia SaridakiFirst Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
Anna KoumarianouHematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University, Athens, Greece.
Elena FountzilasDepartment of Medical Oncology, St Luke's Clinic, Thessaloniki, Greece; European University Cyprus, Engomi, Cyprus. Electronic address: fountzila@oncogenome.gr.
Leonidas BlerisBioengineering Department, The University of Texas at Dallas, Richardson, TX, USA; Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA; Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA. Electronic address: bleris@utdallas.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exceptional responders to targeted cancer therapies offer a unique opportunity to uncover molecular determinants of drug sensitivity. In this study, we aimed to identify genomic alterations associated with exceptional response to cyclin-dependent kinase inhibitors (CDKi) combined with endocrine therapy in individuals with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Sixteen people who achieved prolonged complete or partial responses were retrospectively analyzed using whole-exome sequencing. Among these, six individuals provided high-quality tumor and matched normal blood samples suitable for downstream variant analysis. This cohort exhibited a diverse landscape of germline, somatic, and loss of heterozygosity variants, several of which occurred in genes linked to hormone signaling, cell-cycle regulation, and transcriptional regulation. One shared alteration was a common germline single-nucleotide polymorphism (SNP), rs771205, in the gene MINDY1, a deubiquitylase regulating estrogen receptor alpha (ERα) stability. To explore the functional consequences of this variant, we used CRISPR genome editing to introduce the MINDY1 SNP into breast cancer cell lines. While the variant had no measurable effect on MINDY1 transcript or protein levels, comparative transcriptomic and proteomic profiling associated the variant with alterations in key signaling pathways relevant to palbociclib response. These findings demonstrate how infrequent germline variants can modulate therapeutic response through protein function rather than expression levels. Our work emphasizes the importance of personalized genomic analysis in revealing mechanisms underlying exceptional response, and it highlights MINDY1 as a potential biomarker or co-target in CDK4/6i-treated ER

Indexed as

Breast NeoplasmsCell Cycle ProteinsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Erb-b2 Receptor Tyrosine KinasesPolymorphism, Single NucleotideProtein Kinase InhibitorsAdultAgedCell Line, TumorExome SequencingFemaleHumansMiddle AgedPiperazinesPyridinesCDK4 protein, humanCDK6 protein, humanCell Cycle ProteinsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasespalbociclibPiperazinesProtein Kinase InhibitorsPyridinesReceptors, EstrogenCDK4/6 inhibitorsCRISPR genome editingdisease modelingER+/HER2- breast cancerexceptional respondersMINDY1palbociclibprecision oncologySNPwhole exome sequencing

Identifiers

PMID41449800
PMCPMC12818251

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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.