Evidence map›Paper›PMID 36640300›Full record

SynthesisCell reports2023

A multiplexed in vivo approach to identify driver genes in small cell lung cancer.

Myung Chang Lee, Hongchen Cai, Christopher W Murray, Chuan Li, Yan Ting Shue, Laura Andrejka, Andy L He, Alessandra M E Holzem, Alexandros P Drainas, Julie H Ko and 9 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  3. Article
  4. Article
  5. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. 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

19 authors at 2 institutions in 1 country.

Myung Chang LeeDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Hongchen CaiDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Christopher W MurrayDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Chuan LiDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Yan Ting ShueDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Laura AndrejkaDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Andy L HeDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Alessandra M E HolzemDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Alexandros P DrainasDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Julie H KoDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Garry L ColesDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Christina KongDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Shirley ZhuDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
ChunFang ZhuDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Jason WangDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Matt van de RijnDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Dmitri A PetrovDepartment of Biology, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Monte M WinslowDepartment of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Julien SageDepartment of Pediatrics, Stanford University, 265 Campus Drive, SIM1 G2078, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: julsage@stanford.edu.
Stanford University · USChan Zuckerberg Initiative (United States) · US

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
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
Single-Cell Biology and Data Analysis Shared Resource (SCB-DA SR)U54CA217450 · NCI · VANDERBILT UNIVERSITY · PI WEAVER, ALISSA M · 2018 to 2022
$8.5M
Genomics of rapid adaptation in the lab and in the wildR35GM118165 · NIGMS · STANFORD UNIVERSITY · PI Dmitri Petrov · 2016 to 2026
$8.3M
Investigating molecular and cellular mechanisms of SCLC development to identify novel therapeutic strategiesR35CA231997 · NCI · STANFORD UNIVERSITY · PI SAGE, JULIEN · 2019 to 2025
$6.2M
Unraveling mechanisms of tumor suppression in lung cancerR01CA234349 · NCI · STANFORD UNIVERSITY · PI PETROV, DMITRI, WINSLOW, MONTE MEIER · 2019 to 2023
$2.4M
(PQ4) Quantitative and multiplexed analysis of gene function in cancer in vivoR01CA231253 · NCI · STANFORD UNIVERSITY · PI PETROV, DMITRI, WINSLOW, MONTE MEIER · 2018 to 2022
$2.3M
A Quantitative Multiplexed Platform for the Pharmacogenomic Analysis of Lung CancerR01CA207133 · NCI · STANFORD UNIVERSITY · PI PETROV, DMITRI, WINSLOW, MONTE MEIER · 2016 to 2018
$1.7M
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
Molecular mechanisms of NFIB in small cell lung cancer metastasisF31CA257169 · NCI · STANFORD UNIVERSITY · PI KO, JULIE HYUNJEE · 2021 to 2022
$80k
NCI NIH HHS F31 CA257169NCI NIH HHS P30 CA124435NCI NIH HHS R01 CA207133NCI NIH HHS R01 CA231253NCI NIH HHS R01 CA234349NCI NIH HHS R35 CA231997NCI NIH HHS T32 CA009302NCI NIH HHS U24 CA213274NCI NIH HHS U54 CA217450NCRR NIH HHS S10 RR027431NIGMS NIH HHS R35 GM118165
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) is a lethal form of lung cancer. Here, we develop a quantitative multiplexed approach on the basis of lentiviral barcoding with somatic CRISPR-Cas9-mediated genome editing to functionally investigate candidate regulators of tumor initiation and growth in genetically engineered mouse models of SCLC. We found that naphthalene pre-treatment enhances lentiviral vector-mediated SCLC initiation, enabling high multiplicity of tumor clones for analysis through high-throughput sequencing methods. Candidate drivers of SCLC identified from a meta-analysis across multiple human SCLC genomic datasets were tested using this approach, which defines both positive and detrimental impacts of inactivating 40 genes across candidate pathways on SCLC development. This analysis and subsequent validation in human SCLC cells establish TSC1 in the PI3K-AKT-mTOR pathway as a robust tumor suppressor in SCLC. This approach should illuminate drivers of SCLC, facilitate the development of precision therapies for defined SCLC genotypes, and identify therapeutic targets.

Indexed as

Lung NeoplasmsSmall Cell Lung CarcinomaAnimalsGenes, Tumor SuppressorGenomicsHumansMicePhosphatidylinositol 3-KinasesPhosphatidylinositol 3-KinasesCP: CancerCRISPR screeningfunctional genomicsmeta-analysismouse modelsMTORnaphthaleneSCLCsmall cell lung cancerTSC1tumor suppression

Identifiers

PMID36640300
PMCPMC9972901
OpenAlexW4315926831

What OpenQuestion 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 OpenQuestion graph.