Evidence map›Paper›PMID 38429897›Full record

ArticleHead & neck2024

Differential modulation of PI3K/Akt/mTOR activity by EGFR inhibitors: A rationale for co-targeting EGFR and PI3K in cisplatin-resistant HNSCC.

Jipei Liao, Zejia Yang, Shirin Azarbarzin, Kevin J Cullen, Hancai Dan

Open access · bronzeAbstract read
In one paragraph

Article in Head & neck, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. 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

5 authors at 1 institution in 1 country.

Jipei LiaoUniversity of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Zejia YangUniversity of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Shirin AzarbarzinUniversity of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Kevin J CullenUniversity of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Hancai DanUniversity of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-0332-8290
University of Maryland, Baltimore · US

Funding

UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTERSUPPORT GRANTP30CA134274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI FEYRUZ VIRGILIA RASSOOL · 2008 to 2026
$51.0M
Inhibition of castration resistant prostate cancer by targeting of the IKKbeta/AR signalingR01CA212094 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI DAN, HANCAI · 2017 to 2021
$1.8M
The Role of IKK and NF-kappaB in Controlling mTOR Signaling and TSC ProgressionR00CA149178 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI DAN, HANCAI · 2013 to 2015
$709k
Targeting PI3Kalpha beta and the ErbB family of protein-tyrosine kinases in cisplatin-resistant head and neck squamous cell carcinomas (HNSCC)R56DE030423 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI CULLEN, KEVIN J., DAN, HANCAI · 2022 to 2022
$376k
The Role of IKK and NF-kappaB in Controlling mTOR Signaling and TSC ProgressionK99CA149178 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAN, HANCAI · 2011 to 2012
$164k
NCI NIH HHS K99 CA149178NCI NIH HHS P30 CA134274NCI NIH HHS P30CA134274NCI NIH HHS R00 CA149178NCI NIH HHS R01 CA212094NIDCR NIH HHS R00CA149178NIDCR NIH HHS R01CA212094NIDCR NIH HHS R56 DE030423NIDCR NIH HHS R56DE030423
6 · The paper itself

Abstract

purposeTo find a new strategy to treat cisplatin-resistant head and neck squamous cell carcinoma (HNSCC), we investigated the effects of EGFR inhibitors on the PI3K/Akt/mTOR pathway and determined the efficacy of EGFR inhibitors in combination with PI3K inhibitors to suppress cell proliferation in cisplatin-resistant-HNSCC.

methodsThe cisplatin-resistant HNSCC cell lines were treated with four FDA approved EGFR inhibitors, which included Gefitinb or Erlotinib alone, or in combination with the pan-PI3K inhibitor, BKM120. Phosphorylation and total protein levels of cells were assessed by Western blot analysis. Cell proliferation was examined by MTS assay. Apoptosis was analyzed by flow cytometry.

resultsCisplatin-resistant HNSCC cells were also resistant to EGFR inhibitors. However, a combination of EGFR inhibitors with PI3K inhibitor BKM120 dramatically improved the efficacy of EGFR inhibitors to inhibit cell proliferation and induce apoptosis. Furthermore, treatment with EGFR inhibitors differentially affected the phosphorylation of Akt and mTOR, which included partial inhibition, no inhibition, and induction. A combination of EGFR inhibitors and BKM120 completely blocked phosphorylation of EGFR, Akt, and S6K (an mTOR target).

conclusionOur data provided a rationale for EGFR inhibitors in combination with PI3K inhibitors to treat cisplatin-resistant HNSCC.

Indexed as

AminopyridinesCisplatinHead and Neck NeoplasmsMorpholinesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmErbB ReceptorsHumansPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionSquamous Cell Carcinoma of Head and NeckTOR Serine-Threonine KinasesAminopyridinesCisplatinEGFR protein, humanErbB ReceptorsMorpholinesNVP-BKM120Phosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinasescisplatin resistanceEGFREGFR inhibitorHNSCCPI3KPI3K inhibitorstargeted therapy

Identifiers

PMID38429897
PMCPMC11003831
OpenAlexW4392345883

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.