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Following a change to our organizational structure effective April 1, 2026, this division has been renamed from the "Database Center for Life Science, Joint Support-Center for Data Science Research" to the "Database Division for Life Science (DBCLS), BioData Science Initiative (BSI), National Institute of Genetics (NIG)". Where the former name still appears in the guidelines, please read it as the new name.

Research ID

hum0429-v1Release info

Latest

Research title

CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

Research overview

Aims
Although KRAS G12C inhibitors show clinical activity in patients with KRAS G12C mutated Non-Small Cell Lung Cancer (NSCLC) and other solid tumor malignancies, the response is limited by multiple mechanisms of resistance. The KRAS G12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 ± TNO155, alone or combined with the PI3Kα inhibitor alpelisib and/or the CDK4/6 inhibitor ribociclib, in xenograft models derived from a KRAS G12C-mutant NSCLC cell-line and investigated the genetic mechanisms associated with loss of response to combined KRAS G12C/SHP2 inhibition.
Methods
Low-pass whole-genome sequencing (lp-WGS), RNA-seq
Participants/materials
LU99 tumor-bearing mice treated with either vehicle or quadruple combination regiment (JDQ443 + TNO155 + alpelisib + ribociclib)
URL
N/A

Datasets

CartDataset IDType of dataAnalysis methodAccess criteriaDate published
JGAD000773NGS (WGS, RNA-seq)
  • WGS
  • RNA-seq
Controlled-access (Type I)2023-10-31

Data provider

Principal investigator
Saskia Brachmann
Affiliation
Novartis Institutes for BioMedical Research

Research projects

NameURL
Oncology
N/A

Grants

No grants.

Related publications

TitleDOIDataset ID
CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer
https://doi.org/10.1158/0008-5472.can-23-1127 (opens in a new tab)

Controlled access users

No use of the controlled access data has been recorded.