Evidence map›Paper›PMID 36900375›Full record

ArticleCancers2023

Discovering Synergistic Compounds with BYL-719 in PI3K Overactivated Basal-like PDXs.

David C Boyd, Emily K Zboril, Amy L Olex, Tess J Leftwich, Nicole S Hairr, Holly A Byers, Aaron D Valentine, Julia E Altman, Mohammad A Alzubi, Jacqueline M Grible and 4 more

Open access · goldFull text read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Therapeutic synergies that overcome carboplatin resistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2026
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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

14 authors at 1 institution in 1 country.

David C BoydDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Emily K ZborilDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Amy L OlexC. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0001-8064-521X
Tess J LeftwichDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Nicole S HairrDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-9128-1690
Holly A ByersDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Aaron D ValentineDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-1856-7411
Julia E AltmanDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mohammad A AlzubiDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Jacqueline M GribleDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Scott A TurnerDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Andrea Ferreira-GonzalezDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mikhail G DozmorovDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-0086-8358
J Chuck HarrellDepartment of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-3541-8418
Virginia Commonwealth University · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Renato Martins · 1985 to 2026
$51.0M
Research Supplement to Promote Diversity in Health Related ResearchUL1TR002649 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2018 to 2022
$19.1M
Circumventing acquired carboplatin resistance in triple-negative breast cancersR01CA246182 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI HARRELL, JOSHUA (CHUCK) · 2020 to 2024
$1.9M
NCATS NIH HHS UL1 TR002649NCI NIH HHS 1R01CA246182-01A1NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA246182
6 · The paper itself

Abstract

Basal-like triple-negative breast cancer (TNBC) tumor cells are difficult to eliminate due to resistance mechanisms that promote survival. While this breast cancer subtype has low PIK3CA mutation rates when compared to estrogen receptor-positive (ER+) breast cancers, most basal-like TNBCs have an overactive PI3K pathway due to gene amplification or high gene expression. BYL-719 is a PIK3CA inhibitor that has been found to have low drug-drug interactions, which increases the likelihood that it could be useful for combinatorial therapy. Alpelisib (BYL-719) with fulvestrant was recently approved for treating ER+ breast cancer patients whose cancer had developed resistance to ER-targeting therapy. In these studies, a set of basal-like patient-derived xenograft (PDX) models was transcriptionally defined with bulk and single-cell RNA-sequencing and clinically actionable mutation profiles defined with Oncomine mutational profiling. This information was overlaid onto therapeutic drug screening results. BYL-719-based, synergistic two-drug combinations were identified with 20 different compounds, including everolimus, afatinib, and dronedarone, which were also found to be effective at minimizing tumor growth. These data support the use of these drug combinations towards cancers with activating PIK3CA mutations/gene amplifications or PTEN deficient/PI3K overactive pathways.

Indexed as

afatinibbasal-like breast cancerBYL-719 (alpelisib)dronedaroneeverolimuspatient-derived xenograftprecision medicinesynergismtriple-negative breast cancer

Identifiers

PMID36900375
PMCPMC10001201
OpenAlexW4323314626

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read48
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 Socratic graph.