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Targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma.

ABSTRACT: 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.

SUBMITTER: Vallejo-Diaz J

PROVIDER: S-EPMC5356720 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma.

Vallejo-Díaz Jesús J Olazabal-Morán Manuel M Cariaga-Martínez Ariel E AE Pajares María J MJ Flores Juana M JM Pio Ruben R Montuenga Luis M LM Carrera Ana Clara AC

Oncotarget 20161201 51

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 xenogra ...[more]

PMID: 27835880

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