Evidence map›Paper›PMID 31735913›Full record

ArticleOncogene2020

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma.

Lesley Castillo, Adelaide I J Young, Amanda Mawson, Pia Schafranek, Angela M Steinmann, Danielle Nessem, Ashleigh Parkin, Amber Johns, Angela Chou, Andrew M K Law and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  6. CDK7 inhibition augments response to multidrug chemotherapy in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2022
    Article
  7. Article
  8. NOXA expression drives synthetic lethality to RUNX1 inhibition in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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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

20 authors at 2 institutions in 1 country.

Lesley Castillo *Cancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Adelaide I J Young *Cancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Amanda MawsonCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Pia SchafranekCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Angela M SteinmannCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Danielle NessemCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Ashleigh ParkinCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Amber JohnsCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Angela ChouUniversity of Sydney, Camperdown, NSW, 2006, Australia.
Andrew M K LawCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Morghan C LucasCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Kendelle J MurphyCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Niantao DengCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
David Gallego-OrtegaCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Catherine E CaldonCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Australian Pancreatic Cancer Genome Initiative (APGI)
Paul TimpsonCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Marina PajicCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Christopher J OrmandyCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Samantha R OakesCancer Research Division, Garvan Institute of Medical Research and the Kinghorn Cancer Centre, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia. s.oakes@garvan.org.au.ORCID http://orcid.org/0000-0003-1838-2310
Garvan Institute of Medical Research · AUThe University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies. It is phenotypically heterogeneous with a highly unstable genome and provides few common therapeutic targets. We found that MCL1, Cofilin1 (CFL1) and SRC mRNA were highly expressed by a wide range of these cancers, suggesting that a strategy of dual MCL-1 and SRC inhibition might be efficacious for many patients. Immunohistochemistry revealed that MCL-1 protein was present at high levels in 94.7% of patients in a cohort of PDACs from Australian Pancreatic Genome Initiative (APGI). High MCL1 and Cofilin1 mRNA expression was also strongly predictive of poor outcome in the TCGA dataset and in the APGI cohort. In culture, MCL-1 antagonism reduced the level of the cytoskeletal remodeling protein Cofilin1 and phosphorylated SRC on the active Y416 residue, suggestive of reduced invasive capacity. The MCL-1 antagonist S63845 synergized with the SRC kinase inhibitor dasatinib to reduce cell viability and invasiveness through 3D-organotypic matrices. In preclinical murine models, this combination reduced primary tumor growth and liver metastasis of pancreatic cancer xenografts. These data suggest that MCL-1 antagonism, while reducing cell viability, may have an additional benefit in increasing the antimetastatic efficacy of dasatinib for the treatment of PDAC.

Indexed as

AdenocarcinomaCell Line, TumorDasatinibDrug SynergismHumansMyeloid Cell Leukemia Sequence 1 ProteinNeoplasm InvasivenessPancreatic NeoplasmsDasatinibMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 Protein

Identifiers

PMID31735913
PMCPMC7033042
OpenAlexW2986604169

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.