Evidence map›Paper›PMID 34301758›Full record

ArticleCancer research2021

Lentiviral-Driven Discovery of Cancer Drug Resistance Mutations.

Paul Yenerall, Rahul K Kollipara, Kimberley Avila, Michael Peyton, Christopher A Eide, Daniel Bottomly, Shannon K McWeeney, Yan Liu, Kenneth D Westover, Brian J Druker and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Loss of Payload Sensitivity and Other Mechanisms of Resistance to T-DXd in HER2-Mutant NSCLC: Implications for Subsequent Responsiveness to HER2 TKIs.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
    Article
  3. Article
  4. Upregulation of osteoprotegerin inhibitsExperimental and therapeutic medicine · 2022
    Article
  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

12 authors at 2 institutions in 1 country.

Paul YenerallMcDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas.ORCID 0000-0003-3912-0571
Rahul K KolliparaMcDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas.
Kimberley AvilaHamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas.
Michael PeytonHamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas.
Christopher A EideKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0001-8835-8928
Daniel BottomlyKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
Shannon K McWeeneyKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
Yan LiuDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, Texas.
Kenneth D WestoverDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, Texas.ORCID 0000-0003-3653-5923
Brian J DrukerKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0001-8331-8206
John D MinnaHamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas. ralf.kittler@utsouthwestern.edu john.minna@utsouthwestern.edu.ORCID 0000-0002-7776-0767
Ralf KittlerMcDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas. ralf.kittler@utsouthwestern.edu john.minna@utsouthwestern.edu.ORCID 0000-0002-0098-6792
Southwestern Medical Center · USOregon Health & Science University · US

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4M
UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MELANIE H. COBB · 2010 to 2026
$53.7M
CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATESR01CA065823 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI DRUKER, BRIAN J · 1995 to 2021
$4.7M
Characterization and targeting of rapid nucleotide exchange RAS mutationsR01CA244341 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI WESTOVER, KENNETH · 2020 to 2024
$1.8M
Development of small molecules for ERG ablation in prostate cancerR01CA200787 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI KITTLER, RALF · 2016 to 2020
$1.8M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA142543NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA065823NCI NIH HHS R01 CA200787NCI NIH HHS R01 CA244341
6 · The paper itself

Abstract

Identifying resistance mutations in a drug target provides crucial information. Lentiviral transduction creates multiple types of mutations due to the error-prone nature of the HIV-1 reverse transcriptase (RT). Here we optimized and leveraged this property to identify drug resistance mutations, developing a technique we term LentiMutate. This technique was validated by identifying clinically relevant EGFR resistance mutations, then applied to two additional clinical anticancer drugs: imatinib, a BCR-ABL inhibitor, and AMG 510, a KRAS G12C inhibitor. Novel deletions in BCR-ABL1 conferred resistance to imatinib. In KRAS-G12C or wild-type KRAS, point mutations in the AMG 510 binding pocket or oncogenic non-G12C mutations conferred resistance to AMG 510. LentiMutate should prove highly valuable for clinical and preclinical cancer-drug development. SIGNIFICANCE: LentiMutate can evaluate a drug's on-target activity and can nominate resistance mutations before they occur in patients, which could accelerate and refine drug development to increase the survival of patients with cancer.

Indexed as

Biomarkers, TumorMutationAntineoplastic AgentsCell Line, TumorDose-Response Relationship, DrugDrug DiscoveryDrug Resistance, NeoplasmGene ExpressionGene Expression Regulation, NeoplasticGenetic VectorsHumansLentivirusModels, MolecularNeoplasmsStructure-Activity RelationshipAntineoplastic AgentsBiomarkers, Tumor

Identifiers

PMID34301758
PMCPMC8448967
OpenAlexW3186298983

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.