ArticleNPJ precision oncology2023
AKT/mTOR signaling modulates resistance to endocrine therapy and CDK4/6 inhibition in metastatic breast cancers.
Article in NPJ precision oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Risk of Cardiovascular Events with Cyclin-Dependent Kinases 4 and 6 (CDK 4/6) Inhibitors among Patients with Advanced Breast Cancer: A Systematic Review and Network Meta-Analysis.Reviews in cardiovascular medicine · 2023Pooled it
- Capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer: phase 3 CAPItello-291 study extended Chinese cohort.Nature communications · 2025Trial
- Capivasertib and fulvestrant for patients with HR-positive/HER2-negative advanced breast cancer: analysis of the subgroup of patients from Japan in the phase 3 CAPItello-291 trial.Breast cancer (Tokyo, Japan) · 2025Trial
- Secondary Metabolite Profiling, Antiproliferative Evaluation, and Terpenoid Prioritization of Indonesian Cardamom (Plants (Basel, Switzerland) · 2026Article
- Celecoxib potentiates ribociclib-induced apoptosis and anti-tumor activity by co-targeting COX-2/NF-κB and PI3K/AKT/mTOR pathways in hormone receptor-positive/HER2-negative breast cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4/6 inhibitor-resistant HRCell death & disease · 2026Article
- Metformin Sensitizes HR+/HER2- Breast Cancer Cells to CDK4/6 Inhibitor via Suppressing of PI3K/AKT/mTOR Signaling Pathway.Drug design, development and therapy · 2026Article
- Cardiovascular toxicity of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in HR+/HER2- breast cancer: a real-world study based on the FAERS database.Frontiers in pharmacology · 2026Article
- Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer.Oncology research · 2026Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
- Review
- Ginsenoside Rg5 enhances Abemaciclib sensitivity in ER+ breast cancer by modulating cell cycle proteins via transcriptional and post-translational levels.Journal of ginseng research · 2025Article
- Dual Inhibition of CDK4/6 and mTORC1 Establishes a Preclinical Strategy for Translocation Renal Cell Carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Real-world treatment patterns and outcomes of patients with hormone receptor-positive/HER2-low metastatic breast cancer treated with chemotherapy.The oncologist · 2025Article
- Controllable nickel ions release from deferoxamine mesylate-triggered nickel-iron layered double hydroxide for eliciting apoptotic cell death in prostate cancer.Journal of nanobiotechnology · 2025Article
- Real-time functional proteomics enhances therapeutic targeting in precision oncology molecular tumor boards.NPJ precision oncology · 2025Article
- Application of the Human Proteome in Disease, Diagnosis, and Translation into Precision Medicine: Current Status and Future Prospects.Biomedicines · 2025Review
- PARP12-mediated ADP-ribosylation contributes to breast cancer cell fate by regulating AKT activation and DNA-damage response.Cellular and molecular life sciences : CMLS · 2025Article
- PILRA serves as a diagnostic and prognostic biomarker and modulates the tumor immune microenvironment and immunotherapy response in breast cancer.Frontiers in immunology · 2025Article
- CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment.Frontiers in pharmacology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocrine therapy (ET) in combination with CDK4/6 inhibition is routinely used as first-line treatment for HR+/HER2- metastatic breast cancer (MBC) patients. However, 30-40% of patients quickly develop disease progression. In this open-label multicenter clinical trial, we utilized a hypothesis-driven protein/phosphoprotein-based approach to identify predictive markers of response to ET plus CDK4/6 inhibition in pre-treatment tissue biopsies. Pathway-centered signaling profiles were generated from microdissected tumor epithelia and surrounding stroma/immune cells using the reverse phase protein microarray. Phosphorylation levels of the CDK4/6 downstream substrates Rb (S780) and FoxM1 (T600) were higher in patients with progressive disease (PD) compared to responders (p = 0.02). Systemic PI3K/AKT/mTOR activation in tumor epithelia and stroma/immune cells was detected in patients with PD. This activation was not explained by underpinning genomic alterations alone. As the number of FDA-approved targeted compounds increases, functional protein-based signaling analyses may become a critical component of response prediction and treatment selection for MBC patients.
Identifiers
What Socratic holds
Registered trials
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.