ArticleNature cancer2024
A first-in-class selective inhibitor of EGFR and PI3K offers a single-molecule approach to targeting adaptive resistance.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed.
- Folate-directed morin nano-gold decorated with chitosan: a multifunctional arsenal against triple-negative breast cancer and AMR superbugs.Nanoscale advances · 2026Article
- A first-in-class precision antibody conjugate targeting EGFR, mTOR, and PI3K to treat head and neck cancers.Research square · 2026Article
- Rapid screening of potent and mechanistically insightful repurposable anticancer drugs targeting EGFR for non-small cell lung cancer: machine learning-aided and structure-guided approach.Molecular diversity · 2026Article
- CRISPR Screens Identify PIK3C2A as a Novel Mediator of EGFR Inhibitor Resistance in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- A kinome inhibitor screen implicates adhesion and growth factor signaling in cellular recovery after caspase activation.bioRxiv : the preprint server for biology · 2026Article
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Bioactive Constituents of Ginseng in Cancer Therapy: Molecular Mechanisms, Translational Potential, and Advanced Delivery Strategies.International journal of biological sciences · 2026Review
- Article
- Article
- EGFR-mediated local invasiveness and response to Cetuximab in head and neck cancer.Molecular cancer · 2025Article
- Targeting PI3K Signaling to Overcome Tumor Immunosuppression: Synergistic Strategies to Enhance Cancer Vaccine Efficacy.Vaccines · 2025Review
- A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy.Signal transduction and targeted therapy · 2025Article
- Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.Journal of translational medicine · 2025Review
- Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mutational and co-mutational landscape of early onset colorectal cancer.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Despite tremendous progress in precision oncology, adaptive resistance mechanisms limit the long-term effectiveness of molecularly targeted agents. Here we evaluated the pharmacological profile of MTX-531 that was computationally designed to selectively target two key resistance drivers, epidermal growth factor receptor and phosphatidylinositol 3-OH kinase (PI3K). MTX-531 exhibits low-nanomolar potency against both targets with a high degree of specificity predicted by cocrystal structural analyses. MTX-531 monotherapy uniformly resulted in tumor regressions of squamous head and neck patient-derived xenograft (PDX) models. The combination of MTX-531 with mitogen-activated protein kinase kinase or KRAS-G12C inhibitors led to durable regressions of BRAF-mutant or KRAS-mutant colorectal cancer PDX models, resulting in striking increases in median survival. MTX-531 is exceptionally well tolerated in mice and uniquely does not lead to the hyperglycemia commonly seen with PI3K inhibitors. Here, we show that MTX-531 acts as a weak agonist of peroxisome proliferator-activated receptor-γ, an attribute that likely mitigates hyperglycemia induced by PI3K inhibition. This unique feature of MTX-531 confers a favorable therapeutic index not typically seen with PI3K inhibitors.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.