ArticleThe Journal of experimental medicine2023
MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- A 3D Bioprinted Platform That Maintains the Functional Integrity of Primary AML Cells.Cell proliferation · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Insights from Genomic Sequencing of Preclinical Breast Cancer Models Establish Human Parallels to Increase Therapeutic Applicability.Journal of mammary gland biology and neoplasia · 2026Review
- The mTOR signaling pathway regulates key steps of mammary gland organoid genesis in a temporal manner.Scientific reports · 2026Article
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- Recent Advances in Pineoblastoma Research: Molecular Classification, Modelling and Targetable Vulnerabilities.Cancers · 2025Review
- Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630.Investigational new drugs · 2025Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Invasive lobular carcinoma of the breast: metastatic patterns and treatment modalities-a review.Frontiers in oncology · 2025Review
- Bcl-2 dependent modulation of Hippo pathway in cancer cells.Cell communication and signaling : CCS · 2024Article
- Integrative Analysis of TLS-Associated Gene Signatures, Immune Infiltration and Drug Sensitivity in Pancreatic Cancer.IET systems biologyArticle
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Targeting the PI3K-AKT-mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and development of resistance to PI3K-AKT-mTOR inhibitors remain major clinical challenges. Here, we show that MYC activation drives resistance to mTOR inhibitors (mTORi) in breast cancer. Multiomic profiling of mouse invasive lobular carcinoma (ILC) tumors revealed recurrent Myc amplifications in tumors that acquired resistance to the mTORi AZD8055. MYC activation was associated with biological processes linked to mTORi response and counteracted mTORi-induced translation inhibition by promoting translation of ribosomal proteins. In vitro and in vivo induction of MYC conferred mTORi resistance in mouse and human breast cancer models. Conversely, AZD8055-resistant ILC cells depended on MYC, as demonstrated by the synergistic effects of mTORi and MYCi combination treatment. Notably, MYC status was significantly associated with poor response to everolimus therapy in metastatic breast cancer patients. Thus, MYC is a clinically relevant driver of mTORi resistance that may stratify breast cancer patients for mTOR-targeted therapies.
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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 Socratic graph.