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The association between ERK inhibitor sensitivity and molecular characteristics in colorectal cancer
- Source :
- Biochemical and Biophysical Research Communications. 560:59-65
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful in vitro model system to study cancer, and it has been widely applied for the drug screening. The present study aims to analyze the association between the molecular characteristics which analyzed by next-generation sequencing (NGS) and sensitivity to the ERK inhibitor (i.e., SCH772984) in PDO derived from CRC specimens. A drug sensitivity test for the SCH772984 was conducted using 14 CRC cell lines, and the results demonstrated that the sensitivity was in agreement with the BRAF mutation, but was not completely consistent with the KRAS status. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs but is not necessarily absolutely overlapping. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.
- Subjects :
- Proto-Oncogene Proteins B-raf
0301 basic medicine
MAPK/ERK pathway
Indazoles
endocrine system diseases
Colorectal cancer
Biophysics
Gene mutation
Biology
medicine.disease_cause
Biochemistry
Piperazines
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Exome Sequencing
medicine
Humans
Enzyme Inhibitors
Extracellular Signal-Regulated MAP Kinases
Protein kinase A
neoplasms
Molecular Biology
Mutation
Kinase
High-Throughput Nucleotide Sequencing
Cancer
Cell Biology
medicine.disease
digestive system diseases
Organoids
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
KRAS
Colorectal Neoplasms
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 560
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....324cdca03241bc906f9fa89aecb88193