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Updated: Nov 26, 2025
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Activity-Based Protein Profiling Reveals Potential Dasatinib Targets in Gastric Cancer
Kyoung-Min Choi1, Eunji Cho1, Geul Bang2
1Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon 34134, Korea.
Abstract:
Dasatinib is a multi-target kinase inhibitor, whose targets include BCR-ABL, SRC family kinases, and various cancer kinases. The elevated SRC activity in gastric cancer (GC) has prompted the need for the therapeutic application of dasatinib in GC. We observed that the efficacy of dasatinib varied with the GC cell lines. The differential effect of dasatinib was not correlated with the basal SRC activity of each cell line. Moreover, the GC cell lines showing the strong antitumor effects of dasatinib were refractory to other SRC inhibitors, i.e., bosutinib and saracatinib, suggesting that unexpected dasatinib's targets could exist. To profile the targets of dasatinib in GC, we performed activity-based protein profiling (ABPP) via mass spectrometry using a desthiobiotin-ATP probe. We identified 29 and 18 kinases as potential targets in dasatinib-sensitive (SNU-216, MKN-1) and -resistant (SNU-484, SNU-601) cell lines, respectively. The protein-protein interaction mapping of the differential drug targets in dasatinib-sensitive and -resistant GC using the STRING database suggested that dasatinib could target cellular energy homeostasis in the drug-sensitive GC. RNAi screening for identified targets indicated p90RSK could be a novel dasatinib target, which is important for maintaining the viability and motility of GC cells. Further functional validation of dasatinib off-target actions will provide more effective therapeutic options for GC.
Insights
Dasatinib efficacy varies in gastric cancer (GC) cells, suggesting it targets more than just SRC kinases. Researchers identified p90RSK as a potential novel target, offering new therapeutic avenues for GC.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Elevated SRC activity is observed in gastric cancer (GC), suggesting SRC inhibitors like dasatinib as potential therapies.
- Dasatinib's efficacy in GC is variable and not solely dependent on basal SRC activity.
- Resistance to other SRC inhibitors implies dasatinib may have additional, unexpected targets in GC.
Purpose of the Study:
- To identify the specific kinase targets of dasatinib in gastric cancer.
- To investigate the differential mechanisms of dasatinib action in sensitive versus resistant GC cell lines.
- To explore novel therapeutic targets for GC treatment.
Main Methods:
- Activity-based protein profiling (ABPP) using mass spectrometry with a desthiobiotin-ATP probe to profile dasatinib targets.
- Protein-protein interaction mapping using the STRING database to analyze differential drug targets.
- RNA interference (RNAi) screening to identify novel targets.
Main Results:
- Identified 29 and 18 potential kinase targets in dasatinib-sensitive and -resistant GC cell lines, respectively.
- Protein-protein interaction analysis suggested dasatinib targets cellular energy homeostasis in sensitive GC cells.
- p90RSK was identified as a novel potential dasatinib target crucial for GC cell viability and motility.
Conclusions:
- Dasatinib's variable efficacy in GC is linked to a broader range of kinase targets beyond SRC family kinases.
- p90RSK represents a promising novel therapeutic target for gastric cancer.
- Further validation of dasatinib's off-target effects could lead to improved GC treatment strategies.
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