Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (26013318)
Authors Bonelli MA, Cavazzoni A, Saccani F, Alfieri RR, Quaini F, La Monica S, Galetti M, Cretella D, Caffarra C, Madeddu D, Frati C, Lagrasta CA, Falco A, Rossetti P, Fumarola C, Tiseo M, Petronini PG, Ardizzoni A
Title Inhibition of PI3K Pathway Reduces Invasiveness and Epithelial-to-Mesenchymal Transition in Squamous Lung Cancer Cell Lines Harboring PIK3CA Gene Alterations.
Journal Molecular cancer therapeutics
Vol 14
Issue 8
Date 2015 Aug
URL
Abstract Text A prominent role in the pathogenesis of squamous cell carcinoma of the lung (SQCLC) has been attributed to the aberrant activation of the PI3K signaling pathway, due to amplification or mutations of the p110α subunit of class I phosphatidylinositol 3-kinase (PIK3CA) gene. The aim of our study was to determine whether different genetic alterations of PIK3CA affect the biologic properties of SQCLC and to evaluate the response to specific targeting agents in vitro and in vivo. The effects of NVP-BEZ235, NVP-BKM120, and NVP-BYL719 on two-dimensional/three-dimensional (2D/3D) cellular growth, epithelial-to-mesenchymal transition, and invasiveness were evaluated in E545K or H1047R PIK3CA-mutated SQCLC cells and in newly generated clones carrying PIK3CA alterations, as well as in a xenograft model. PIK3CA mutated/amplified cells showed increased growth rate and enhanced migration and invasiveness, associated with an increased activity of RhoA family proteins and the acquisition of a mesenchymal phenotype. PI3K inhibitors reverted this aggressive phenotype by reducing metalloproteinase production, RhoA activity, and the expression of mesenchymal markers, with the specific PI3K inhibitors NVP-BKM120 and NVP-BYL719 being more effective than the dual PI3K/mTOR inhibitor NVP-BEZ235. A xenograft model of SQCLC confirmed that PIK3CA mutation promotes the acquisition of a mesenchymal phenotype in vivo and proved the efficacy of its specific targeting drug NVP-BYL719 in reducing the growth and the expression of mesenchymal markers in xenotransplanted tumors. These data indicate that PIK3CA mutation/amplification may represent a good predictive feature for the clinical application of specific PI3K inhibitors in SQCLC patients.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA H1047R lung squamous cell carcinoma sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA H1047R in culture (PMID: 26013318). 26013318
PIK3CA over exp lung squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type Pik3ca in culture (PMID: 26013318). 26013318
PIK3CA H1047R lung squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA H1047R in culture (PMID: 26013318). 26013318
PIK3CA H1047R lung squamous cell carcinoma sensitive Buparlisib Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type Pik3ca in culture (PMID: 26013318). 26013318
PIK3CA E545K lung squamous cell carcinoma sensitive Buparlisib Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA E545K in culture (PMID: 26013318). 26013318
PIK3CA E545K lung squamous cell carcinoma sensitive Dactolisib Preclinical - Cell culture Actionable In a preclinical study, BEZ235 induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA E545K in culture (PMID: 26013318). 26013318
PIK3CA over exp lung squamous cell carcinoma sensitive Buparlisib Preclinical - Cell culture Actionable In a preclinical study, Buparlisib (BKM120) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type Pik3ca in culture (PMID: 26013318). 26013318
PIK3CA over exp lung squamous cell carcinoma sensitive Alpelisib Preclinical - Cell line xenograft Actionable In a preclinical study, Alpelisib (BYL719) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing wild-type PIK3CA in culture, and inhibited tumor growth in cell line xenograft models (PMID: 26013318). 26013318
PIK3CA E545K lung squamous cell carcinoma sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) induced apoptosis, inhibited cell proliferation, migration, and invasion of lung squamous cell carcinoma cells over expressing PIK3CA E545K in culture (PMID: 26013318). 26013318