ArticleCancer discovery2024
INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.
What it found
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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
76 citing papers in PubMed, 100 citations in OpenAlex.
- Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial.Nature communications · 2026Trial
- A Phase II Study of Abemaciclib for Patients with Retinoblastoma-Positive, Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Next-generation CDK inhibitors in HR+/HER2- breast cancer.The Journal of clinical investigation · 2026Review
- Recent advances in Pyrazolo[3,4-d]pyrimidine-based dual inhibitors in the treatment of cancers.Molecular diversity · 2026Review
- Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- An Integrated Computational Workflow for Discovering Alkaloid-Derived Ligands of Cyclin-Dependent Kinase 2.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Lethal clinical outcome and immune desert contexture in refractory gastric cancer harboring CCNE1 amplification and overexpression.British journal of cancer · 2026Article
- The Pan-Tumor Landscape of Gene Amplifications and Copy Number Amplification Ratio for Established and Emerging Clinical Targets.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Machine Learning and Virtual Screening Methods to Discover Potential Cyclin-Dependent Kinase 2 (CDK2) Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Mechanisms of lactylation-related biomarker in neonatal hypoxic-ischemic brain damage analyzed through multi-omics data.Pediatric research · 2026Article
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- Beyond CDK4/6 Inhibition: Current Strategies in Hormone Receptor-Positive Metastatic Breast Cancer.Current treatment options in oncology · 2026Review
- Novel indole-based scaffolds: Design, synthesis, molecular modeling, and anti-proliferative evaluation.BMC chemistry · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Cyclin-dependent kinase 2 (CDK2) is thought to play an important role in driving proliferation of certain cancers, including those harboring CCNE1 amplification and breast cancers that have acquired resistance to CDK4/6 inhibitors (CDK4/6i). The precise impact of pharmacologic inhibition of CDK2 is not known due to the lack of selective CDK2 inhibitors. Here we describe INX-315, a novel and potent CDK2 inhibitor with high selectivity over other CDK family members. Using cell-based assays, patient-derived xenografts (PDX), and transgenic mouse models, we show that INX-315 (i) promotes retinoblastoma protein hypophosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth; (ii) overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control while reinstating the chromatin architecture of CDK4/6i-induced TIS; and (iii) delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets. Our results support the clinical development of selective CDK2 inhibitors. SIGNIFICANCE: INX-315 is a novel, selective inhibitor of CDK2. Our preclinical studies demonstrate activity for INX-315 in both CCNE1-amplified cancers and CDK4/6i-resistant breast cancer. In each case, CDK2 inhibition induces cell cycle arrest and a phenotype resembling cellular senescence. Our data support the development of selective CDK2 inhibitors in clinical trials. See related commentary by Watts and Spencer, p. 386. This article is featured in Selected Articles from This Issue, p. 384.
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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.