Evidence map›Paper›PMID 40886461›Full record

ArticleGynecologic oncology2025

Efficacy of cyclin-dependent kinase 4/6 inhibitors in preclinical adult-type ovarian granulosa cell tumor models.

Allison L Brodsky, Thomas Welte, Veena K Vuttaradhi, Xue Yang, Elio Tahan, Eleonora Khlebus, J Celestino, Reid T Powell, Clifford C Stephan, Nghi Nguyen and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gynecologic oncology, 2025. 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. 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

18 authors.

Allison L BrodskyDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Thomas WelteDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Veena K VuttaradhiDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xue YangGraduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Elio TahanDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Eleonora KhlebusDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J CelestinoDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Reid T PowellTexas A&M Health Center for Translational Cancer Research, Houston, TX, USA.
Clifford C StephanTexas A&M Health Center for Translational Cancer Research, Houston, TX, USA.
Nghi NguyenTexas A&M Health Center for Translational Cancer Research, Houston, TX, USA.
Yimin GengResearch Medical Library, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jian LiDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shiro TakamatsuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Katherine CalzoncinthDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lauren CobbDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David M GershensonDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Barrett LawsonDepartment of Anatomic Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
R Tyler HillmanUniversity of California San Diego, Rebecca and John Moores Cancer Center, Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, La Jolla, CA, USA. Electronic address: rthillman@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Training of Academic Gynecologic OncologistsT32CA101642 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIL K SOOD, Kathleen Schmeler · 2005 to 2026
$9.2M
NCI NIH HHS P30 CA016672NCI NIH HHS T32 CA101642
6 · The paper itself

Abstract

backgroundCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve outcomes in metastatic, hormone receptor-positive breast cancer and low-grade serous ovarian carcinoma. Adult granulosa cell tumors (AGCTs) are similarly hormonally active tumors. We aimed to determine whether CDK4/6i were effective in pre-clinical models of AGCTs.

methodsPre-clinical models used in this study include the KGN cell line, in cell culture and mouse models, and multiple novel AGCT tumoroids treated with CDK4/6i, including abemaciclib. Half-maximal inhibitory concentration (IC50) was used to assess potency of drugs. Cell number was determined using CCK8 cytotoxicity assay. Mice were treated with daily gavage with control or abemaciclib. Patients with AGCTs and prior CDK4/6i treatment were identified retrospectively.

resultsCDK4/6i demonstrated high potency in KGN cells with an IC50 value of 50 nM for abemaciclib. Adding fulvestrant to abemaciclib did not significantly affect cell proliferation. Abemaciclib demonstrated proliferation inhibition in seven AGCT tumoroids. The xenograft model demonstrated significant differences in tumor volume (p = 0.003) and tumor mass (p = 0.0002) after treatment with abemaciclib or vehicle control. Eleven patients with AGCT who received CDK4/6i treatment were identified. Best responses included partial response (3, 27.3 %), stable disease (6, 54.5 %), and progressive disease (2, 18.2 %). The median duration of response was 6 months. The regimen was well tolerated.

conclusionsCDK4/6i demonstrated potent inhibition of tumor cell proliferation in multiple preclinical models. CDK4/6i demonstrated tolerability and effectiveness in a small cohort of patients with AGCT. This data supports the design of clinical trials to test the efficacy of CDK4/6i in the treatment of recurrent AGCT.

Indexed as

AminopyridinesBenzimidazolesCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Granulosa Cell TumorOvarian NeoplasmsProtein Kinase InhibitorsAdultAnimalsCell Line, TumorFemaleFulvestrantHumansMiceMiddle AgedRetrospective StudiesabemaciclibAminopyridinesBenzimidazolesCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6FulvestrantProtein Kinase InhibitorsAbemaciclibAdult granulosa cell tumorCDK4/6 inhibitorsGranulosa cell tumorKGN

Identifiers

PMID40886461
PMCPMC12614906

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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.