Evidence map›Paper›PMID 41867770›Full record

ArticlebioRxiv : the preprint server for biology2026

Deep Learning Enabled 3D Multi-Omic Analysis Reveals Molecular Signatures of Heterogeneous Response to Chemotherapy in Pancreatic Cancer.

André Forjaz, Hengameh Mojdeganlou, Alens Valentin, Meredith Wetzel, Dmitrijs Lvovs, Atul Deshpande, Sarah M Shin, Sujan Piya, Kimal I Rajapakshe, Paola A Guerrero and 22 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

32 authors.

André ForjazDepartment of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.ORCID 0009-0002-5115-2293
Hengameh MojdeganlouDepartment of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Alens ValentinDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0009-0003-4348-4527
Meredith WetzelDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0009-0005-6955-3521
Dmitrijs LvovsInstitute for Genome Sciences, University of Maryland, Baltimore, MD.ORCID 0009-0003-2152-6853
Atul DeshpandeDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0000-0001-5144-6924
Sarah M ShinDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0000-0002-7423-0090
Sujan PiyaDepartment of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-8976-540X
Kimal I RajapaksheDepartment of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-0472-858X
Paola A GuerreroDepartment of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
Brian A PedroDepartment of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Dimitrios N SidiropoulosDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0000-0001-5716-3917
Pei-Hsun WuThe Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD.ORCID 0000-0002-7371-2960
Vincent Bernard PaganDepartment of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
Demystifying Pancreatic Cancer Therapies TeamLab
Denis WirtzDepartment of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.ORCID 0000-0001-6147-3045
Elana J FertigInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD.ORCID 0000-0003-3204-342X
Luciane T KagoharaDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0000-0003-1706-0950
Won Jin HoDepartment of Oncology, Johns Hopkins University, Baltimore, MD.ORCID 0000-0003-2644-5086
Ashley L KiemenDepartment of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.ORCID 0000-0002-6281-2616
Laura D WoodDepartment of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Eric S ChristensonDepartment of Oncology, Johns Hopkins University, Baltimore, MD.
William A Freed-PastorDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Christine A Iacobuzio-DonahueHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Rachel KarchinThe Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD 21218, USA.
Elias-Ramzey KarnoubHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Anirban MaitraDepartments of Pathology and Medicine, New York University Grossman School of Medicine and Perlmutter Cancer Center, New York, NY, USA.
Jerry MelchorHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Wungki ParkDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Valentina Matos-RomeroDepartment of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD.
Eileen O'ReillyDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
Kevin C SoaresDavid M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.

Funding

Tech Core 2U54CA268083 · NCI · JOHNS HOPKINS UNIVERSITY · PI Pei-Hsun wu · 2022 to 2026
$10.2M
Opportunities for Pathology Trainees in Cancer ResearchT32CA193145 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A., EBERHART, CHARLES G · 2015 to 2025
$2.6M
Informing mechanistic rules of agent-based models with single-cell multi-omicsU24CA284156 · NCI · TRUSTEES OF INDIANA UNIVERSITY · PI Elana Fertig, Paul T Macklin · 2024 to 2026
$2.3M
Elucidating the molecular and cellular mechanisms of immune evasion in pancreatic cancerK08CA259621 · NCI · DANA-FARBER CANCER INST · PI WILLIAM A FREED-PASTOR · 2022 to 2026
$1.1M
Mass Cytometer CyTOF XT for Single-Cell BiologyS10OD034407 · OD · JOHNS HOPKINS UNIVERSITY · PI HO, WON JIN · 2024 to 2024
$499k
NCI NIH HHS K08 CA259621NCI NIH HHS T32 CA193145NCI NIH HHS U24 CA284156NCI NIH HHS U54 CA268083NIH HHS S10 OD034407
6 · The paper itself

Abstract

Resistance to systemic therapy is a major unmet challenge in pancreatic cancer. To identify potential mechanisms of resistance, we developed a novel 3D pipeline in clinical samples that uses deep learning to classify sensitive and persistent tumor cell populations based on morphological features, enabling subsequent molecular characterization of intratumoral heterogeneity. We applied this automated 3D pipeline to a cohort of human pancreatic cancer samples treated with neoadjuvant chemotherapy, identifying heterogeneity in response to therapy both between and within tumors. Application of spatial proteomics to these sensitive and persistent regions identified enhanced epithelial-to-mesenchymal transition and non-classical cell states in persistent cells, confirming our morphological classification. Integration of spatial transcriptomics in multiple pancreatic cancer cohorts associated fibroblast-cancer crosstalk via syndecans with resistance to cytotoxic therapy. Our validated 3D multi-omic pipeline is now poised for application to clinical trials, enabling discovery of resistance mechanisms and design of new therapeutic combinations to circumvent resistance.

Identifiers

PMID41867770
PMCPMC13001410

What OpenQuestion holds

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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.