ArticleMolecular cancer therapeutics2015
Combined Inhibition of Cyclin-Dependent Kinases (Dinaciclib) and AKT (MK-2206) Blocks Pancreatic Tumor Growth and Metastases in Patient-Derived Xenograft Models.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01783171 (A Phase I Trial of Dinaciclib), which is not on this map. Cited by 45 papers, 1 of them a synthesis 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.
A Phase I Trial of Dinaciclib (SCH727965) and MK-2206 in Metastatic Pancreatic Cancer With an Expansion Cohort in Advanced Pancreatic Cancer
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Pooled it
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Novel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer.Cell death & disease · 2025Article
- Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer.International journal of molecular sciences · 2024Review
- Recent advances in drug delivery and targeting for the treatment of pancreatic cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Article
- Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?Therapeutic advances in medical oncology · 2024Review
- Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review).Oncology reports · 2023Review
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- Estimating Metastatic Risk of Pancreatic Ductal Adenocarcinoma at Single-Cell Resolution.International journal of molecular sciences · 2022Article
- A Preclinical and Phase Ib Study of Palbociclib plus Nab-Paclitaxel in Patients with Metastatic Adenocarcinoma of the Pancreas.Cancer research communications · 2022Article
- Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects.International journal of molecular sciences · 2022Review
- Emerging kinase inhibitors for the treatment of pancreatic ductal adenocarcinoma.Expert opinion on emerging drugs · 2022Review
- Review
- Synthetic lethality of cyclin-dependent kinase inhibitor Dinaciclib withCell cycle (Georgetown, Tex.) · 2022Article
- Review
- CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation.Cancer medicine · 2021Article
- Review
- Extracellular Vesicle Delivery of TRAIL Eradicates Resistant Tumor Growth in Combination with CDK Inhibition by Dinaciclib.Cancers · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
KRAS is activated by mutation in the vast majority of cases of pancreatic cancer; unfortunately, therapeutic attempts to inhibit KRAS directly have been unsuccessful. Our previous studies showed that inhibition of cyclin-dependent kinase 5 (CDK5) reduces pancreatic cancer growth and progression, through blockage of the centrally important RAL effector pathway, downstream of KRAS. In the current study, the therapeutic effects of combining the CDK inhibitor dinaciclib (SCH727965; MK-7965) with the pan-AKT inhibitor MK-2206 were evaluated using orthotopic and subcutaneous patient-derived human pancreatic cancer xenograft models. The combination of dinaciclib (20 mg/kg, i.p., three times a week) and MK-2206 (60 mg/kg, orally, three times a week) dramatically blocked tumor growth and metastasis in all eight pancreatic cancer models examined. Remarkably, several complete responses were induced by the combination treatment of dinaciclib and MK-2206. The striking results obtained in these models demonstrate that the combination of dinaciclib with the pan-AKT inhibitor MK-2206 is promising for therapeutic evaluation in pancreatic cancer, and strongly suggest that blocking RAL in combination with other effector pathways downstream from KRAS may provide increased efficacy in pancreatic cancer. Based on these data, an NCI-CTEP-approved multicenter phase I clinical trial for pancreatic cancer of the combination of dinaciclib and MK-2206 (NCT01783171) has now been opened.
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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.