NBDC Research ID: hum0429.v1
SUMMARY
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)
| Dataset ID | Type of Data | Criteria | Release Date |
|---|---|---|---|
| JGAS000643 | NGS（WGS, RNA-seq） | Controlled-access (Type I) | 2023/11/13 |
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MOLECULAR DATA
| Participants/Materials |
tumor tissue collected from LU99 tumor-bearing mice: total 16 samples tumor tissue collected from mice with treatment (JDQ443 + TNO155 + alpelisib + ribociclib) / vehicle condition at 3 hours / 24 hours after the last dose: 4 samples each |
| Targets | WGS |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | DNAs extracted from tumor tissues |
| Cell Lines | https://cellbank.brc.riken.jp/cell_bank/CellInfo/?cellNo=RCB1900 |
| Library Construction (kit name) | NEBNext Ultra II DNA PCR-free Library Prep Kit for Illumina |
| Fragmentation Methods | Ultrasonic fragmentation (Covaris) |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 51 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000773 |
| Total Data Volume | 85.9 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials |
tumor tissue collected from LU99 tumor-bearing mice: total 16 samples tumor tissue collected from mice with treatment (JDQ443 + TNO155 + alpelisib + ribociclib) / vehicle condition at 3 hours / 24 hours after the last dose: 4 samples each |
| Targets | RNA-seq |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | RNAs extracted from tumor tissues |
| Cell Lines | https://cellbank.brc.riken.jp/cell_bank/CellInfo/?cellNo=RCB1900 |
| Library Construction (kit name) | Illumina Stranded Total RNA Prep, Ligation with Ribo-Zero Plus |
| Fragmentation Methods | Enzymatic fragmentation |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 50 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000773 |
| Total Data Volume | 85.9 GB (fastq) |
| Comments (Policies) | NBDC policy |
DATA PROVIDER
Principal Investigator: Saskia Brachmann
Affiliation: Novartis Institutes for BioMedical Research
Project / Group Name: Oncology
Funds / Grants (Research Project Number):
| Name | Title | Project Number |
|---|---|---|
PUBLICATIONS
| Title | DOI | Dataset ID | |
|---|---|---|---|
| 1 | CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer | doi: 10.1158/0008-5472.CAN-23-1127 | JGAD000773 |
USRES (Controlled-access Data)
| Principal Investigator | Affiliation | Country/Region | Research Title | Data in Use (Dataset ID) | Period of Data Use |
|---|---|---|---|---|---|
