Evidence mapPaperPMID 40565304Full record

ArticleInternational journal of molecular sciences2025

Functional Analysis of the PI3K/AKT/mTOR Pathway Inhibitor, Gedatolisib, Plus Fulvestrant with and Without Palbociclib in Breast Cancer Models.

Aaron Broege, Stefano Rossetti, Adrish Sen, Ann De La Forest, Laura Davis, Megan Seibel, Arul S Menon, Sydney Stokke, Allison Macaulay, Jhomary Molden and 1 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Trial
  2. Review
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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

11 authors.

Aaron BroegeCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Stefano RossettiCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Adrish SenCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.ORCID 0009-0002-8081-3425
Ann De La ForestCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Laura DavisCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Megan SeibelCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Arul S MenonCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.ORCID 0009-0008-7552-3195
Sydney StokkeCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Allison MacaulayCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Jhomary MoldenCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.
Lance LaingCelcuity, Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN 55446, USA.ORCID 0000-0003-4593-0685

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment with endocrine therapy (ET) in combination with CDK4/6 inhibitors has improved the outcome of patients with hormone receptor (HR)+/HER2- advanced breast cancer (ABC), but most patients eventually experience disease progression. Since the PI3K-AKT-mTOR (PAM), estrogen receptor (ER), and cyclin-dependent kinase (CDK) pathways are interdependent drivers of HR+/HER2- breast cancer (BC), the simultaneous inhibition of these pathways is expected to enhance anti-tumor control. Here we investigated the molecular and cellular effects of gedatolisib, a multi-target kinase inhibitor of the PAM pathway currently being evaluated in Phase 3 clinical trials, combined with fulvestrant and/or palbociclib in BC cell models. We found that the gedatolisib/fulvestrant/palbociclib triplet inhibited BC cell growth significantly more than the single agents or the palbociclib/fulvestrant doublet, both in vitro and vivo. Specifically, the triplet combination counteracted adaptive responses associated with single drug treatment, such as the reactivation of the CDK-RB-E2F pathway after palbociclib treatment, and inhibited multiple cellular functions, such as cell cycle progression, cell survival, protein synthesis, and glucose metabolism. The triplet combination was effective in treatment-naïve BC cell lines as well as in cell lines adapted to palbociclib and/or fulvestrant, regardless of

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFulvestrantPiperazinesProto-Oncogene Proteins c-aktPyridinesTOR Serine-Threonine KinasesAnimalsCell Line, TumorCell ProliferationFemaleHumansMicePhosphatidylinositol 3-KinasesSignal TransductionXenograft Model Antitumor AssaysFulvestrantMTOR protein, humanpalbociclibPhosphatidylinositol 3-KinasesPiperazinesProto-Oncogene Proteins c-aktPyridinesTOR Serine-Threonine Kinasesbreast cancerCDK4/6 inhibitorsendocrine therapyfulvestrantgedatolisibpalbociclibPI3K-AKT-mTOR inhibitors

Identifiers

PMID40565304
PMCPMC12193243

What Socratic holds

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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 Socratic graph.