Evidence map›Paper›PMID 29303405›Full record

ArticleCancer biology & therapy2018

Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma.

Rajani Kanteti, Tamara Mirzapoiazova, Jacob J Riehm, Immanuel Dhanasingh, Bolot Mambetsariev, Jiale Wang, Prakash Kulkarni, Garima Kaushik, Parthasarathy Seshacharyulu, Moorthy P Ponnusamy and 4 more

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

Article in Cancer biology & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
8.5field-weighted citation impact, top 1% 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

60 citing papers in PubMed, 97 citations in OpenAlex.

  1. Trial
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  13. Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?International journal of molecular sciences · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Chemotherapy treatment induces pro-invasive changes in liver ECM composition.Matrix biology : journal of the International Society for Matrix Biology · 2022
    Article
  19. Article
  20. The Development of FAK Inhibitors: A Five-Year Update.International journal of molecular sciences · 2022
    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

14 authors at 4 institutions in 2 countries.

Rajani Kantetia Department of Hematology/Oncology , University of Chicago Medical Center , Chicago , IL , USA.
Tamara Mirzapoiazovab Department of Medical Oncology and Therapeutics Research , City of Hope, Duarte , CA , USA.
Jacob J Riehma Department of Hematology/Oncology , University of Chicago Medical Center , Chicago , IL , USA.
Immanuel Dhanasingha Department of Hematology/Oncology , University of Chicago Medical Center , Chicago , IL , USA.
Bolot Mambetsarievb Department of Medical Oncology and Therapeutics Research , City of Hope, Duarte , CA , USA.
Jiale Wangb Department of Medical Oncology and Therapeutics Research , City of Hope, Duarte , CA , USA.
Prakash Kulkarnib Department of Medical Oncology and Therapeutics Research , City of Hope, Duarte , CA , USA.
Garima Kaushikc Department of Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , NE , USA.
Parthasarathy Seshacharyuluc Department of Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , NE , USA.
Moorthy P Ponnusamyc Department of Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , NE , USA.
Hedy L Kindlera Department of Hematology/Oncology , University of Chicago Medical Center , Chicago , IL , USA.
Mohd W Nasserc Department of Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , NE , USA.
Surinder K Batrac Department of Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , NE , USA.
Ravi Salgiaa Department of Hematology/Oncology , University of Chicago Medical Center , Chicago , IL , USA.
University of Chicago Medical Center · USUniversity of Nebraska Medical Center · USCity of Hope · USSouthern Medical University · CN

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
NCI NIH HHS P30 CA033572
6 · The paper itself

Abstract

The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.

Indexed as

AnimalsBenzamidesCarcinoma, Pancreatic DuctalCell AdhesionCell Culture TechniquesCell Line, TumorCell MovementFocal Adhesion Kinase 1Focal Adhesion Kinase 2HumansLung NeoplasmsMesotheliomaMesothelioma, MalignantMiceMice, TransgenicNeoplasms, Experimental6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-oneBenzamidesdefactinibFocal Adhesion Kinase 1Focal Adhesion Kinase 2Hras protein, mouseProto-Oncogene Proteins p21(ras)PTK2B protein, humanPTK2 protein, humanPyrazinesQuinolonesSulfonamidesSulfonesFAKmesotheliomapancreatic cancerPF-431396PF-573228VS-6063

Identifiers

PMID29303405
PMCPMC5902231
OpenAlexW2781878830

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.