ReviewNature reviews. Drug discovery2015
The history and future of targeting cyclin-dependent kinases in cancer therapy.
Review in Nature reviews. Drug discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 893 papers, 4 of them syntheses that pooled it.
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.
PAveMenT: Phase Ib Study of Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer
A Randomised Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer
Who cites it
893 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,738 citations in OpenAlex.
- Considerations for establishing occupational exposure limits for small molecule kinase inhibitors in drug development.Frontiers in toxicology · 2026Pooled it
- Efficacy of cyclin-dependent kinases 4 and 6 inhibitors in the treatment of HR +/HER2 - advanced breast cancer: a meta-analysis.European journal of medical research · 2025Pooled it
- Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2- metastatic breast cancer.European journal of clinical pharmacology · 2024Pooled it
- Dual inhibitors of CDK2 and TRKA kinases: design, synthesis, antiproliferative activity and molecular modeling of novel pyrazolopyrimidine derivatives.RSC advances · 2026Article
- Design, synthesis, anticancer estimation, and computational studies of novel benzochromenoimidazopyrimidines as CDK-2 inhibitors and apoptosis stimulators.Molecular diversity · 2026Article
- Targeting casein kinase 1α-mediated FADD phosphorylation restores sensitivity in select CDK4/6 inhibitor-resistant breast cancer models.The Journal of clinical investigation · 2026Article
- Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma.Biomedicines · 2026Review
- The mechanism of malignant progression in extramammary Paget's disease (EMPD): hallmarks of EMPD.Medical molecular morphology · 2026Review
- Time-resolved proteomic and phosphoproteomic analysis reveals convergent and divergent biological perturbations induced by FDA-approved CDK4/6 inhibitors in hormone receptor-positive breast cancers.Acta pharmacologica Sinica · 2026Article
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Design, Synthesis, Biological Activity Evaluation, and Molecular Docking of 2-Aminopyrimidine-Based PKMYT1 Inhibitors.Biomedicines · 2026Article
- An Integrated Computational Workflow for Discovering Alkaloid-Derived Ligands of Cyclin-Dependent Kinase 2.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- An immunohistochemical based assessment of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) in jaw osteosarcoma and benign osseous lesions.Oral and maxillofacial surgery · 2026Article
- Discovery of CTX-439: A Potent and Selective CDK12 Inhibitor as a Prospective Anti-Cancer Drug.ACS medicinal chemistry letters · 2026Article
- Pyridine Derivatives as Cyclin-Dependent Kinase Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2026Article
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Cyclin-dependent kinase-inhibitor screening and structural analysis identify a CDK-like kinase candidate in Naegleria fowleri.Parasites & vectors · 2026Article
833 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Cancer represents a pathological manifestation of uncontrolled cell division; therefore, it has long been anticipated that our understanding of the basic principles of cell cycle control would result in effective cancer therapies. In particular, cyclin-dependent kinases (CDKs) that promote transition through the cell cycle were expected to be key therapeutic targets because many tumorigenic events ultimately drive proliferation by impinging on CDK4 or CDK6 complexes in the G1 phase of the cell cycle. Moreover, perturbations in chromosomal stability and aspects of S phase and G2/M control mediated by CDK2 and CDK1 are pivotal tumorigenic events. Translating this knowledge into successful clinical development of CDK inhibitors has historically been challenging, and numerous CDK inhibitors have demonstrated disappointing results in clinical trials. Here, we review the biology of CDKs, the rationale for therapeutically targeting discrete kinase complexes and historical clinical results of CDK inhibitors. We also discuss how CDK inhibitors with high selectivity (particularly for both CDK4 and CDK6), in combination with patient stratification, have resulted in more substantial clinical activity.
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.