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YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib

Irati Garmendia1,2, María J Pajares1,2,3,4, Francisco Hermida-Prado3,5

  • 1Program in Solid Tumors, Center for Applied Medical Research, Pamplona, Spain.

American Journal of Respiratory and Critical Care Medicine
|June 6, 2019
PubMed

Insights

YES1 alterations drive non-small cell lung cancer (NSCLC) growth and metastasis. Targeting YES1 with dasatinib shows promise, with YES1 status acting as a biomarker for effective NSCLC therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Personalized therapies for non-small cell lung cancer (NSCLC) require identification of novel genetic alterations and stratification biomarkers.
  • The SRC family kinase YES1 is frequently altered in lung cancer, suggesting its potential role in tumorigenesis.

Purpose of the Study:

  • To investigate YES1 as a therapeutic target and predictive biomarker for dasatinib response in NSCLC.
  • To evaluate the functional role of YES1 in NSCLC progression and metastasis.

Main Methods:

  • Utilized in vivo NSCLC and metastasis models, patient-derived xenografts, and in vitro functional assays.
  • Assessed the efficacy of pharmacological and genetic (CRISPR/Cas9) YES1 abrogation.
  • Analyzed the association between YES1 alterations and clinical prognosis in patient samples.

Main Results:

  • YES1 is crucial for NSCLC carcinogenesis and metastasis, with overexpression promoting tumor spread.
  • YES1 depletion via CRISPR/Cas9 significantly inhibited tumor growth and metastasis, primarily through mTOR signaling.
  • YES1 amplifications conferred sensitivity to dasatinib, identifying YES1 status as a predictive biomarker.
  • High YES1 protein expression independently predicted poor prognosis in lung cancer patients.

Conclusions:

  • YES1 represents a promising therapeutic target for lung cancer.
  • YES1 status can serve as a predictive biomarker for selecting NSCLC patients who may benefit from dasatinib therapy, supporting its clinical evaluation.
Keywords:
Src family kinasesYES1dasatiniblung cancerpredictive biomarker

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