Evidence map›Paper›PMID 40848256›Full record

ArticleCell reports2025

Integrative genomic identification of therapeutic targets for pancreatic cancer.

Jimmy A Guo, Dennis Gong, Kyle Evans, Kazuki Takahashi, Ananya D Jambhale, Carina Shiau, Patrick Yu, Steven Wang, Wenbo W Wu, Seema Chugh and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
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

20 authors.

Jimmy A GuoBroad Institute of MIT and Harvard, Cambridge, MA, USA; School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Dennis GongBroad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts Institute of Technology, Cambridge, MA, USA; Center for Systems Biology, Krantz Family Center for Cancer Research, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
Kyle EvansBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Kazuki TakahashiBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Ananya D JambhaleGrossman School of Medicine, New York University, New York, NY, USA.
Carina ShiauHarvard Medical School, Boston, MA, USA.
Patrick YuUniversity of Washington, Seattle, WA, USA.
Steven WangStanford University, Stanford, CA, USA.
Wenbo W WuHarvard Medical School, Boston, MA, USA.
Seema ChughBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kevin S KapnerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Julien DillyBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Daniel ZhaoNew York Medical College, Valhalla, NY, USA.
Peter ChenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Eric L SmithDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Joseph D ManciasHarvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Francisca VazquezBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Harshabad SinghDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
William L HwangBroad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Systems Biology, Krantz Family Center for Cancer Research, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: whwang1@mgh.harvard.edu.
Andrew J AguirreBroad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: andrew_aguirre@dfci.harvard.edu.

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI MAYER, ROBERT J · 2007 to 2023
$33.2M
Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivityU01CA274276 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre, Stephanie Dougan · 2022 to 2026
$5.1M
Mechanisms of response and resistance to KRAS inhibition in pancreatic cancerR01CA276268 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre · 2023 to 2026
$2.2M
Elucidating cancer-intrinsic mechanisms of perineural invasion in pancreatic cancerK08CA270417 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI William L Hwang · 2022 to 2026
$1.6M
NCI NIH HHS K08 CA270417NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA276268NCI NIH HHS U01 CA274276
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, and new therapeutic strategies are urgently needed. Here, we conduct an integrative, genome-scale examination of genetic dependencies and cell surface targets using CRISPR-Cas screening and multi-omic data, including single-nucleus and spatial transcriptomic data from patient tumors. We systematically identify clinically tractable and biomarker-linked PDAC dependencies, including CDS2 as a synthetic lethal target in cancer cells expressing signatures of epithelial-to-mesenchymal transition. We examine biomarkers and co-dependencies of the KRAS oncogene, defining gene expression signatures of sensitivity and resistance associated with response to pharmacological inhibition of KRAS. mRNA and protein profiling reveal cell surface protein-encoding genes with robust expression in patient tumors and minimal expression in non-malignant tissues. Furthermore, we define intratumoral and interpatient heterogeneity of target gene expression and identify orthogonal targets that suggest combinatorial strategies. Collectively, this work identifies multiple targets that may inform therapeutic strategies for patients with PDAC.

Indexed as

Carcinoma, Pancreatic DuctalGenomicsPancreatic NeoplasmsBiomarkers, TumorCell Line, TumorEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansMolecular Targeted TherapyProto-Oncogene Proteins p21(ras)Biomarkers, TumorProto-Oncogene Proteins p21(ras)biomarkerscancer dependency mapCDS2CP: CancerCP: Genomicsmulti-omicspancreatic cancertherapeutic targets

Identifiers

PMID40848256
PMCPMC12807561

What OpenQuestion holds

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Registered trials

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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.