Evidence map›Paper›PMID 26774265›Full record

ArticleBMC cancer2016

FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine.

Dannel Yeo, Hong He, Oneel Patel, Andrew M Lowy, Graham S Baldwin, Mehrdad Nikfarjam

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
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

32 citing papers in PubMed, 53 citations in OpenAlex.

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  6. [Computer-aided prediction and molecular mechanism investigation of active components in compound Kushen injection inhibiting p21-activated kinase 1].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2024
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  10. Targeting p21-activated kinase 1 for development of a novel anti-arrhythmic drug class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
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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 at 3 institutions in 2 countries.

Dannel YeoDepartment of Surgery, Austin Health, University of Melbourne, Heidelberg, VIC, Australia. yeod@student.unimelb.edu.au.
Hong HeDepartment of Surgery, Austin Health, University of Melbourne, Heidelberg, VIC, Australia. hong.he@unimelb.edu.au.
Oneel PatelDepartment of Surgery, Austin Health, University of Melbourne, Heidelberg, VIC, Australia. patelo@unimelb.edu.au.
Andrew M LowyDepartment of Surgery, Division of Surgical Oncology, University of California at San Diego, Moores Cancer, La Jolla, CA, USA. alowy@ucsd.edu.au.
Graham S BaldwinDepartment of Surgery, Austin Health, University of Melbourne, Heidelberg, VIC, Australia. grahamsb@unimelb.edu.au.
Mehrdad NikfarjamDepartment of Surgery, Austin Health, University of Melbourne, Heidelberg, VIC, Australia. mehrdad.nikfarjam@gmail.com.
Austin Health · AUUniversity of California, San Diego · USUniversity of Melbourne · AU

Funding

RON Receptor in Pancreatic Cancer Biology and TherapyR01CA155620 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOWY, ANDREW M · 2011 to 2021
$2.9M
NCI NIH HHS CA155620-01NCI NIH HHS R01 CA155620
6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumours. Treatment options are limited and gemcitabine-based chemotherapy remains the standard of care. Although growing evidence shows that p21-activated kinase 1 (PAK1) plays a crucial role in pancreatic cancer, its role has not been fully elucidated. This study aimed to characterise the expression and functional relevance of PAK1 in pancreatic cancer.

methodsPAK1 expression was measured in pancreatic cancer specimens by immunohistochemistry and in pancreatic cancer cell lines by western blotting. The effect of inhibition of PAK1 by either shRNA knock-down (KD), or by a selective inhibitor, FRAX597, alone or in combination with gemcitabine, on cell proliferation and migration/invasion was measured by thymidine uptake and Boyden chamber assays, respectively. The effect on tumour growth and survival was assessed in orthotopic murine models.

resultsPAK1 was expressed in all human pancreatic cancer samples tested, an7d was upregulated in all pancreatic cancer cell lines tested. PAK1 KD inhibited pancreatic cancer cell growth and survival, and increased sensitivity to gemcitabine treatment. AKT activity and HIF1α expression were also inhibited. FRAX597 inhibited pancreatic cancer cell proliferation, survival, and migration/invasion. When combined with gemcitabine, FRAX597 synergistically inhibited pancreatic cancer proliferation in vitro and inhibited tumour growth in vivo.

conclusionsThese results implicate PAK1 as a regulator of pancreatic cancer cell growth and survival. Combination of a PAK1 inhibitor such as FRAX597 with cytotoxic chemotherapy deserves further study as a novel therapeutic approach to pancreatic cancer treatment.

Indexed as

Drug SynergismAdenocarcinomaAnimalsCell Line, TumorCell MovementCell ProliferationDeoxycytidineGemcitabineHumansMiceNeoplasm Invasivenessp21-Activated KinasesPancreatic DuctsPancreatic NeoplasmsPyridonesPyrimidinesDeoxycytidineFRAX597Gemcitabinep21-Activated KinasesPAK1 protein, humanPyridonesPyrimidines

Identifiers

PMID26774265
PMCPMC4715347
OpenAlexW2265788461

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.