Targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma
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Jesús Vallejo-Díaz1, Manuel Olazabal-Morán1, Ariel E. Cariaga-Martínez1, María J. Pajares2,4,5, Juana M. Flores3, Ruben Pio2,4,6, Luis M. Montuenga2,4,5, Ana Clara Carrera1
1Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Universidad Autónoma de Madrid, Cantoblanco, Madrid
2Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain
3Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Spain
4Navarra Health Research Institute (IDISNA), University of Navarra, Pamplona, Spain
5Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain
6Department of Biochemistry and Genetics, School of Science, University of Navarra, Pamplona, Spain
Ana Clara Carrera, email: [email protected]
Keywords: lung cancer, SQCC, PIK3R2, targeted therapy, PI3K pathway
Received: March 02, 2016 Accepted: October 21, 2016 Published: November 08, 2016
Oncogenic mutations in the PI3K/AKT pathway are present in nearly half of human tumors. Nonetheless, inhibitory compounds of the pathway often induce pathway rebound and tumor resistance. We find that lung squamous cell carcinoma (SQCC), which accounts for ~20% of lung cancer, exhibits increased expression of the PI3K subunit PIK3R2, which is at low expression levels in normal tissues. We tested a new approach to interfere with PI3K/AKT pathway activation in lung SQCC. We generated tumor xenografts of SQCC cell lines and examined the consequences of targeting PIK3R2 expression. In tumors with high PIK3R2 expression, and independently of PIK3CA, KRAS, or PTEN mutations, PIK3R2 depletion induced lung SQCC xenograft regression without triggering PI3K/AKT pathway rebound. These results validate the use PIK3R2 interfering tools for the treatment of lung squamous cell carcinoma.
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