ArticleNPJ breast cancer2020
Mechanism of action biomarkers predicting response to AKT inhibition in the I-SPY 2 breast cancer trial.
Article in NPJ breast cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 35 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
- Tumor heterogeneity index from DCE-MRI for AKT-inhibition responder identification and reveals hot immune microenvironment for patients with breast cancer: a multi-omics analysis of I-SPY2 trial.Breast cancer research : BCR · 2026Article
- Proteomics in Antitumor Drug Target Discovery, Toxicity, Resistance, and Precision Oncology.Drug design, development and therapy · 2026Review
- Tumor Imaging Heterogeneity Index-Inspired Insights into the Unveiling Tumor Microenvironment of Breast Cancer.International journal of molecular sciences · 2025Article
- Immune Subtyping Identifies Patients With Hormone Receptor-Positive Early-Stage Breast Cancer Who Respond to Neoadjuvant Immunotherapy (IO): Results From Five IO Arms of the I-SPY2 Trial.JCO precision oncology · 2025Article
- Real-time functional proteomics enhances therapeutic targeting in precision oncology molecular tumor boards.NPJ precision oncology · 2025Article
- 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
- Hormone Receptor-Positive HER2-Negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple-Negative Breast Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Laser capture microdissection.Nature reviews. Methods primers · 2025Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer.Cancers · 2024Review
- Harnessing the potential of reverse-phase protein array technology: Advancing precision oncology strategies.Cancer science · 2024Review
- Endogenous pAKT activity is associated with response to AKT inhibition alone and in combination with immune checkpoint inhibition in murine models of TNBC.Cancer letters · 2024Article
- Targeting HER2/HER3 co-mutations in metastatic breast cancer: Case reports of exceptional responders to trastuzumab and pertuzumab therapy.Cancer reports (Hoboken, N.J.) · 2024Article
- Protein signaling and drug target activation signatures to guide therapy prioritization: Therapeutic resistance and sensitivity in the I-SPY 2 Trial.Cell reports. Medicine · 2023Article
- AKT/mTOR signaling modulates resistance to endocrine therapy and CDK4/6 inhibition in metastatic breast cancers.NPJ precision oncology · 2023Article
- Analysis of neuroendocrine clones in NSCLCs using an immuno-guided laser-capture microdissection-based approach.Cell reports methods · 2022Article
- Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies.Cancer cell · 2022Article
- Characterization of anticancer drug resistance by reverse-phase protein array: new targets and strategies.Expert review of proteomics · 2022Review
- Evolving Evidence for the Optimization of Neoadjuvant Therapy in Triple-Negative Breast Cancer.Breast cancer : basic and clinical research · 2022Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
The AKT inhibitor MK2206 (M) was evaluated in I-SPY 2 and graduated in the HER2+, HR-, and HR- HER2+ signatures. We hypothesized that AKT signaling axis proteins/genes may specifically predict response to M and tested 26 phospho-proteins and 10 genes involved in AKT-mTOR-HER signaling; in addition, we tested 9 genes from a previous study in the metastatic setting. One hundred and fifty patients had gene expression data from pretreatment biopsies available for analysis (M: 94, control: 56) and 138 had protein data (M: 87, control: 51). Logistic modeling was used to assess biomarker performance in pre-specified analysis. In general, phospho-protein biomarkers of activity in the AKT-mTOR-HER pathway appeared more predictive of response to M than gene expression or total protein biomarkers in the same pathway; however, the nature of the predictive biomarkers differed in the HER2+ and TN groups. In the HER2+ subset, patients achieving a pCR in M had higher levels of multiple AKT kinase substrate phospho-proteins (e.g., pmTOR, pTSC2). In contrast, in the TN subset responding patients had lower levels of AKT pathway phospho-proteins, such as pAKT, pmTOR, and pTSC2. Pathway mutations did not appear to account for these associations. Additional exploratory whole-transcriptome analysis revealed immune signaling as strongly associated with response to M in the HER2+ subset. While our sample size is small, these results suggest that the measurement of particular AKT kinase substrate phospho-proteins could be predictive of MK2206 efficacy in both HER2+ and TN tumors and that immune signaling may play a role in response in HER2+ patients.
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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 OpenQuestion graph.