ArticleCancer discovery2023
SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed.
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- New Treatment Strategy and Future Research Direction for BRAF-Mutated Cancer.Cancer science · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Screening of tyrosine phosphatase SHP2 (PTPN11) inhibitors from natural products with therapeutic potential for receptor tyrosine kinase-driven cancer.Journal of pharmaceutical analysis · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Daytime SHP2 inhibitor dosing, when immune cell numbers are elevated, shrinks neurofibromas.Life science alliance · 2025Article
- Allosteric SHP2 inhibitors suppress lung cancer cell migration by inhibiting non-canonical activation of EphA2 via the ERK-RSK signaling pathway.Scientific reports · 2025Article
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- Targeting PDGFRA-SHP2 signaling enhances radiotherapy in IDH1-mutant glioma.Neuro-oncology · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Review
- Integrated multi-omics identify key signalling pathways for notochord lumenogenesis in ascidianOpen biology · 2025Article
- First Results of Migoprotafib, a Potent and Highly Selective Src Homology-2 Domain-Containing Phosphatase 2 Inhibitor in Patients with Advanced Solid Tumors.Molecular cancer therapeutics · 2025Article
- KRASMolecular oncology · 2025Article
- Tumor suppressor function of formyl peptide receptor 1 in gastrointestinal cancers: a focus on the underlying signaling.Frontiers in cell and developmental biology · 2025Review
- Alectinib combined with cobimetinib in ALK-Rearranged lung Cancer: A phase IB study.Lung cancer (Amsterdam, Netherlands) · 2025Article
- Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance.International journal of molecular sciences · 2024Review
- TNO155 is a selective SHP2 inhibitor to targetHeliyon · 2024Article
- Mechanisms of Response and Tolerance to Active RAS Inhibition in KRAS-Mutant Non-Small Cell Lung Cancer.Cancer discovery · 2024Article
Corrections and comments
- Commented on by
Authors and funding
25 authors.
Funding
Abstract
Rationally targeted therapies have transformed cancer treatment, but many patients develop resistance through bypass signaling pathway activation. PF-07284892 (ARRY-558) is an allosteric SHP2 inhibitor designed to overcome bypass-signaling-mediated resistance when combined with inhibitors of various oncogenic drivers. Activity in this setting was confirmed in diverse tumor models. Patients with ALK fusion-positive lung cancer, BRAFV600E-mutant colorectal cancer, KRASG12D-mutant ovarian cancer, and ROS1 fusion-positive pancreatic cancer who previously developed targeted therapy resistance were treated with PF-07284892 on the first dose level of a first-in-human clinical trial. After progression on PF-07284892 monotherapy, a novel study design allowed the addition of oncogene-directed targeted therapy that had previously failed. Combination therapy led to rapid tumor and circulating tumor DNA (ctDNA) responses and extended the duration of overall clinical benefit. SIGNIFICANCE: PF-07284892-targeted therapy combinations overcame bypass-signaling-mediated resistance in a clinical setting in which neither component was active on its own. This provides proof of concept of the utility of SHP2 inhibitors in overcoming resistance to diverse targeted therapies and provides a paradigm for accelerated testing of novel drug combinations early in clinical development. See related commentary by Hernando-Calvo and Garralda, p. 1762. This article is highlighted in the In This Issue feature, p. 1749.
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.