Evidence map›Paper›PMID 40985049›Full record

ArticleHead & neck2026

CRISPR Screens Identify PIK3C2A as a Novel Mediator of EGFR Inhibitor Resistance in Head and Neck Squamous Cell Carcinoma.

Jiayu Wang, Megan L Ludwig, Aditi Kulkarni, Andrew C Birkeland, Nicole L Michmerhuizen, Elizabeth Gensterblum-Miller, Jingyi Zhai, Hui Jiang, Paul Swiecicki, Marisa Buchakjian and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Head & neck, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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.

Jiayu WangDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Megan L LudwigDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Aditi KulkarniDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Andrew C BirkelandDepartment of Otolaryngology-Head and Neck Surgery, University of California, Davis, California, USA.
Nicole L MichmerhuizenDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Elizabeth Gensterblum-MillerDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Jingyi ZhaiDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Hui JiangDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Paul SwiecickiRogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.
Marisa BuchakjianDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Molly Heft NealDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.ORCID 0000-0002-8813-5537
Steven B ChinnDepartment of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Matthew E SpectorUniversity of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Chad BrennerDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.ORCID 0000-0003-3238-1111

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Cellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1M
Dissecting Co-Dependent Pathways in Oral CancersU01DE025184 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BRENNER, JOHN CHADWICK, CAREY, THOMAS E. · 2015 to 2018
$3.7M
Defining the Role of HPV Integration Structures in HNSCC Molecular HeterogeneityR01DE032699 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner, RYAN E MILLS · 2024 to 2026
$1.8M
Investigating the Mechanisms of Resistance to EGFR-Targeted Therapy in Head and Neck Squamous Cell CarcinomaF31CA206341 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUDWIG, MEGAN LOREE · 2017 to 2019
$93k
American Cancer Society R01DE032699American Cancer Society T32GM145470National Science Foundation DGE-1256260NCI NIH HHS F31 CA206341NCI NIH HHS P30 CA046592NIDCR NIH HHS F31 CA206341-03NIDCR NIH HHS R01 DE032699NIDCR NIH HHS U01 DE025184NIGMS NIH HHS T32 GM145470NIH HHS P30-CA046592NIH HHS U01DE025184
6 · The paper itself

Abstract

backgroundHead and neck squamous cell carcinoma (HNSCC) is a malignancy with poor prognosis and survival. While epidermal growth factor receptor (EGFR) is a known driver of HNSCC, EGFR inhibitors show limited efficacy as monotherapies, suggesting that effective combination therapies are needed.

methodsWe performed GeCKO and Kinase CRISPR library screens to identify candidate knockouts that increase EGFR inhibitor sensitivity in resistant HNSCC cells. We validated a candidate using the CellTiter-Glo viability assay following RNA interference and investigated the mechanisms using apoptosis and cell cycle flow cytometry analysis.

resultsKinase CRISPR library screens identified that PIK3C2A gene downregulation enhanced EGFR inhibitor sensitivity in resistant HNSCC cells. Viability assays further validated that PIK3C2A knockdown overcame EGFR inhibitor resistance in HNSCC cells.

conclusionsOur data suggests that PIK3C2A is a novel mediator of EGFR inhibitor resistance in HNSCC. Future studies are required to determine the mechanisms by which PIK3C2A drives EGFR inhibitor resistance.

Indexed as

Drug Resistance, NeoplasmErbB ReceptorsHead and Neck NeoplasmsPhosphatidylinositol 3-KinasesSquamous Cell Carcinoma of Head and NeckAntineoplastic AgentsApoptosisCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsHumansProtein Kinase InhibitorsAntineoplastic AgentsEGFR protein, humanErbB ReceptorsPhosphatidylinositol 3-Kinasesphosphoinositol-3 kinase regulatory subunit 2, humanProtein Kinase InhibitorsCRISPRdrug resistanceEGFR inhibitorHNSCCPIK3C2A

Identifiers

PMID40985049
PMCPMC12797014

What Socratic 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 Socratic graph.