Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 54 citations in OpenAlex.
- Immune and Growth Factor Signaling Pathways Are Associated with Pathologic Complete Response to an Anti-Type I Insulin-like Growth Factor Receptor Regimen in Patients with Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- 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 in Hormone Receptor-Positive Advanced Breast Cancer.The New England journal of medicine · 2023Trial
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- (+)-Miliusol suppresses the Warburg effect and induces regulated cell death in triple-negative breast cancer through targeting EIF3D and remodeling cancer metabolism.Acta pharmaceutica Sinica. B · 2026Article
- [Breast cancer research : BCR · 2026Article
- Targeting the UFL1-AKT cascade suppresses triple-negative breast cancer progression.Nature communications · 2026Article
- Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer.Oncology research · 2026Review
- Current and Future Landscape of Hepatocellular Carcinoma Treatment.Oncology research · 2026Review
- Ipatasertib in Patients with Tumors with AKT Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1K.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- PRKG1 hinders myogenic differentiation and predicts response to AKT inhibitor ipatasertib in Rhabdomyosarcoma.Nature communications · 2025Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
- UBE2S inhibits colorectal cancer proliferation by regulating the PI3K/AKT and MAPK/ERK pathways via TRAF6.Scientific reports · 2025Article
- The EGFR Pathway as a Potential Therapeutic Target for Modulation of Radiation-induced Liver Injury.Radiation research · 2025Article
- Real-time functional proteomics enhances therapeutic targeting in precision oncology molecular tumor boards.NPJ precision oncology · 2025Article
- Comprehensive Molecular and Genomic Analysis of NCI-MATCH Subprotocol Y: Capivasertib in Patients With anJCO precision oncology · 2025Article
- Use of metabolic imaging to monitor heterogeneity of tumour response following therapeutic mTORC1/2 pathway inhibition.Disease models & mechanisms · 2025Article
- Laser capture microdissection.Nature reviews. Methods primers · 2025Article
- Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort.British journal of cancer · 2024Article
- Personalized medicine: Clinical oncology on molecular view of treatment.World journal of clinical oncology · 2024Review
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Authors and funding
18 authors at 12 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDespite extensive genomic and transcriptomic profiling, it remains unknown how signaling pathways are differentially activated and how tumors are differentially sensitized to certain perturbations. Here, we aim to characterize AKT signaling activity and its association with other genomic or IHC-based PI3K/AKT pathway biomarkers as well as the clinical activity of ipatasertib (AKT inhibitor) in the FAIRLANE trial. EXPERIMENTAL
designIn FAIRLANE, 151 patients with early triple-negative breast cancer (TNBC) were randomized 1:1 to receive paclitaxel with ipatasertib or placebo for 12 weeks prior to surgery. Adding ipatasertib did not increase pathologic complete response rate and numerically improved overall response rate by MRI. We used reverse-phase protein microarrays (RPPA) to examine the total level and/or phosphorylation states of over 100 proteins in various signaling or cell processes including PI3K/AKT and mTOR signaling. One hundred and twenty-five baseline and 127 on-treatment samples were evaluable by RPPA, with 110 paired samples at both time points.
resultsTumors with genomic/protein alterations in PIK3CA/AKT1/PTEN were associated with higher levels of AKT phosphorylation. In addition, phosphorylated AKT (pAKT) levels exhibited a significant association with enriched clinical benefit of ipatasertib, and identified patients who received benefit in the absence of PIK3CA/AKT1/PTEN alterations. Ipatasertib treatment led to a downregulation of AKT/mTORC1 signaling, which was more pronounced among the tumors with PIK3CA/AKT1/PTEN alterations or among the responders to the treatment.
conclusionsWe showed that the high baseline pAKT levels are associated with the alterations of PI3K/AKT pathway components and enriched benefit of ipatasertib in TNBC.
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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.