Evidence map›Paper›PMID 41279637›Full record

ArticlebioRxiv : the preprint server for biology2025

YAP1 defines an emergent, plastic population of relapsed small cell lung cancer.

C Allison Stewart, Kavya Ramkumar, Runsheng Wang, Yuanxin Xi, Alexa Halliday, Lixia Diao, Qi Wang, Alejandra Serrano, Sarah Groves, Simon Heeke and 14 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

24 authors.

C Allison StewartDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-7758-1179
Kavya RamkumarDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Runsheng WangDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yuanxin XiDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexa HallidayDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lixia DiaoDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Qi WangDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alejandra SerranoDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX USA.
Sarah GrovesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA USA.
Simon HeekeDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Azusa TanimotoDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Laura KaiserDepartment of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Whitney LewisDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mukulika BoseDepartment of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pedro Da RochaDepartment of Medical Oncology, Thoracic Tumors Unit, Vall d'Hebron University Hospital, Barcelona, Spain.
Loukia KaracostaDepartment of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vito QuarantaInstitute for Experiential AI, Northeastern University, Boston, MA, USA.
Jing WangDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Julie GeorgeDepartment of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Luisa Maren Solis SotoDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX USA.
Bingnan ZhangDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John V HeymachDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lauren A ByersDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Carl M GayDepartment of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V. · 1996 to 2024
$57.4M
Coordinating center for the NCI small cell lung cancer research consortiumU24CA213274 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Lauren Averett Byers, JOHN D. MINNA · 2017 to 2026
$12.9M
TRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8M
Therapeutic strategies for targeting PARP1 in small cell lung cancerR01CA207295 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Lauren Averett Byers · 2016 to 2026
$3.7M
Novel therapeutic approaches for enhancing anti-tumor immunity in SCLCU01CA213273 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BYERS, LAUREN AVERETT, HEYMACH, JOHN V. · 2017 to 2021
$3.0M
Molecular and immunological heterogeneity of Small Cell Lung Cancer (SCLC) and its impact on relapse and therapeutic responseU01CA256780 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BYERS, LAUREN AVERETT, HEYMACH, JOHN V. · 2021 to 2025
$3.0M
NovaSeq6000S10OD024977 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUFF, VICKI · 2018 to 2018
$995k
Detection and elimination of drug tolerant persister cells in small cell lung cancerR01CA299261 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Carl Michael Gay · 2025 to 2026
$850k
Modeling tumor heterogeneity, to develop new therapeutic strategies for treatment of resistant small cell lung cancerR50CA243698 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Catherine Allison Stewart · 2020 to 2026
$701k
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA207295NCI NIH HHS R01 CA299261NCI NIH HHS R50 CA243698NCI NIH HHS T32 CA009666NCI NIH HHS U01 CA213273NCI NIH HHS U01 CA256780NCI NIH HHS U24 CA213274NIH HHS S10 OD024977
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by rapid onset of chemoresistance and poor clinical outcomes. Transcriptional heterogeneity among treatment-naïve SCLC tumors underlies four transcriptional subtypes, each with distinct clinical vulnerabilities. Though previously hypothesized to delineate a distinct subtype, expression of YAP1 is largely absent from treatment-naïve, pure SCLC. To characterize relapsed SCLC, circulating tumor DNA, circulating tumor cells, and core needle biopsies from SCLC patients and preclinical models following resistance to standard-of-care therapies were analyzed. In contrast to treatment-naïve SCLC, these analyses reveal an emergent YAP1-positive cell population that coincides with treatment resistance. These YAP1-positive cells exhibit characteristics of drug tolerant persister cells, including senescence, stemness, and plasticity, as YAP1 positive cells largely abandon features characteristic of SCLC to adopt those of large-cell neuroendocrine carcinoma (LCNEC). As a result of this SCLC-like to LCNEC-like evolution,

Indexed as

intratumoral heterogeneityplasticitySCLCYAP1

Identifiers

PMID41279637
PMCPMC12633449

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.