Evidence map›Paper›PMID 41213213›Full record

ArticleOral oncology2025

Integrating artificial intelligence-driven digital pathology and genomics to establish patient-derived organoids as new approach methodologies for drug response in head and neck cancer.

Rose Doerfler, Jie Chen, Carl Kim, Joshua D Smith, Micah Harris, Krishna B Singh, Brian Isett, Rebekah E Dadey, Daniel D Brown, Adrian V Lee and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oral oncology, 2025. 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
–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

14 citing papers in PubMed.

  1. Article
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  6. Article
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  9. Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors.

Rose DoerflerHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Jie ChenHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Cancer Bioinformatics Core, UPMC, Pittsburgh, PA, USA.
Carl KimHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Joshua D SmithHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Micah HarrisHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Krishna B SinghHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Brian IsettHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Cancer Bioinformatics Core, UPMC, Pittsburgh, PA, USA.
Rebekah E DadeyHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Daniel D BrownInstitute for Precision Medicine, UPMC, Pittsburgh, PA, USA.
Adrian V LeeInstitute for Precision Medicine, UPMC, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Xuefeng WangBiostatistics and Bioinformatics Program and Immuno-Oncology Program, Moffitt Cancer Center, Tampa, FL, USA.
Matthew E SpectorHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Seungwon KimHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Shaum SridharanHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Kevin ContreraHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Katelyn SmithHillman Cancer Center, UPMC, Pittsburgh, PA, USA.
Carly ReederHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Maureen LyonsHillman Cancer Center, UPMC, Pittsburgh, PA, USA.
Jianhua LuoDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Silvia LiuOrgan Pathobiology and Therapeutics Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Dan P ZandbergHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Heath D SkinnerHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ioannis K ZervantonakisHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Lazar VujanovićHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Robert L FerrisHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
Raja R SeethalaHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
José P ZevallosHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Jason J LukeHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Division of Malignant Hematology and Medical Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
Riyue BaoHillman Cancer Center, UPMC, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Division of Malignant Hematology and Medical Oncology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: baor@upmc.edu.

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Heath Devin Skinner · 2004 to 2026
$49.6M
Training in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2M
Immune Exclusion in Cancer ImmunotherapyR01DE031729 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Riyue Bao, Dan Paul Zandberg · 2022 to 2026
$3.0M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA097190NCI NIH HHS T32 CA082084NIDCR NIH HHS R01 DE031729NIH HHS S10 OD028483
6 · The paper itself

Abstract

Patient-derived organoids (PDOs) emerge as advanced 3D ex vivo New Approach Methodologies (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumor's pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor versus normal PDOs in culture using digital histopathology images (AUC ≥ 0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs retained the corresponding p53 functional status as confirmed by IHC (enhanced or loss of protein expression). Somatic mutational landscape revealed that PDOs preserved driver somatic mutations, copy number variations (CNVs), and clonal architecture including low-prevalence subclones. Drug sensitivity assessment of PDOs showed that cisplatin reduced cell viability, whereas cetuximab and lenvatinib had minimal effects. Chemoradiation led to greater tumor organoid killing compared to radiation or chemotherapy alone. This study presents an integrated HNSCC PDO platform combining tissue biobanking, organoid establishment, multiomics characterization, functional drug screening, and AI-driven histopathologic classification, providing a comprehensive and scalable system for translational cancer research.

Indexed as

Artificial IntelligenceGenomicsHead and Neck NeoplasmsOrganoidsSquamous Cell Carcinoma of Head and NeckFemaleHumansMaleArtificial intelligenceCNNDigital pathologyDrug responseGenomicsHead and neck cancerHuman specimensNew approach methodologiesOrganoidsTransfer learning

Identifiers

PMID41213213
PMCPMC13262258

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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.