Evidence map›Paper›PMID 39123441›Full record

ArticleCancers2024

Synergistic Efficacy of CDK4/6 Inhibitor Abemaciclib and HDAC Inhibitor Panobinostat in Pancreatic Cancer Cells.

Shraddha Bhutkar, Anjali Yadav, Himaxi Patel, Shrikant Barot, Ketan Patel, Vikas V Dukhande

Abstract read
In one paragraph

Article in Cancers, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Shraddha BhutkarDepartment of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA.ORCID 0000-0002-0137-4528
Anjali YadavDepartment of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA.ORCID 0000-0001-7355-6411
Himaxi PatelDepartment of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA.
Shrikant BarotDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-0924-5701
Ketan PatelDepartment of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA.ORCID 0000-0001-8252-0234
Vikas V DukhandeDepartment of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, St. John's University, Queens, NY 11439, USA.ORCID 0000-0002-9288-715X

Funding

Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma TreatmentR16GM145557 · NIGMS · ST. JOHN'S UNIVERSITY · PI DUKHANDE, VIKAS VASUDEO · 2022 to 2025
$656k
NIGMS NIH HHS 5R16GM145557-03NIGMS NIH HHS R16 GM145557
6 · The paper itself

Abstract

The current 5-year survival rate of pancreatic cancer is about 12%, making it one of the deadliest malignancies. The rapid metastasis, acquired drug resistance, and poor patient prognosis necessitate better therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC). Multiple studies show that combining chemotherapeutics for solid tumors has been successful. Targeting two distinct emerging hallmarks, such as non-mutational epigenetic changes by panobinostat (Pan) and delayed cell cycle progression by abemaciclib (Abe), inhibits pancreatic cancer growth. HDAC and CDK4/6 inhibitors are effective but are prone to drug resistance and failure as single agents. Therefore, we hypothesized that combining Abe and Pan could synergistically and lethally affect PDAC survival and proliferation. Multiple cell-based assays, enzymatic activity experiments, and flow cytometry experiments were performed to determine the effects of Abe, Pan, and their combination on PDAC cells and human dermal fibroblasts. Western blotting was used to determine the expression of cell cycle, epigenetic, and apoptosis markers. The Abe-Pan combination exhibited excellent efficacy and produced synergistic effects, altering the expression of cell cycle proteins and epigenetic markers. Pan, alone and in combination with Abe, caused apoptosis in pancreatic cancer cells. Abe-Pan co-treatment showed relative safety in normal human dermal fibroblasts. Our novel combination treatment of Abe and Pan shows synergistic effects on PDAC cells. The combination induces apoptosis, shows relative safety, and merits further investigation due to its therapeutic potential in the treatment of PDAC.

Indexed as

abemaciclibcell cycledrug synergyepigeneticspancreatic cancerpanobinostat

Identifiers

PMID39123441
PMCPMC11311278

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Registered trials

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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.