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YES1 Is a Druggable Oncogenic Target in SCLC
Esther Redin1, Eva M Garrido-Martin2, Karmele Valencia3
1Program in Solid Tumors, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Oncología (CIBERONC), The Carlos III Health Institute (ISCIII), Madrid, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Navarra, Spain; Department of Pathology, Anatomy, and Physiology, School of Medicine, University of Navarra, Pamplona, Spain.
YES1 is a novel oncogene driving small cell lung cancer (SCLC) growth and metastasis. Targeting YES1 with inhibitors shows promise for treating SCLC patients, with circulating YES1 acting as a potential biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Small cell lung cancer (SCLC) is an aggressive cancer with limited targeted therapy options.
- Identifying novel oncogenes is crucial for developing new SCLC treatments.
Purpose of the Study:
- To identify and characterize novel targetable oncogenes in SCLC.
- To evaluate YES1 as a therapeutic target and biomarker in SCLC.
Main Methods:
- YES1 expression and its association with prognosis in SCLC clinical samples.
- In vitro functional assays (proliferation, apoptosis, cell cycle, cytotoxicity).
- In vivo studies using xenografts and metastasis models; evaluation of YES1 in plasma exosomes.
Main Results:
- YES1 overexpression/amplification found in 31%/26% of SCLC cases, predicting poor prognosis.
- YES1 inhibition reduced proliferation, tumor growth, and metastasis, inducing apoptosis.
- YES1 blockade with CH6953755 or dasatinib showed antitumor activity.
- Circulating YES1 in plasma exosomes may serve as a biomarker.
Conclusions:
- YES1 is a druggable oncogenic target in a subset of SCLC patients.
- Targeting YES1 offers a potential new therapeutic strategy for SCLC.
- YES1 in exosomes can be a biomarker for patient selection and monitoring.
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