Reference Detail

Ref Type

Journal Article

PMID

(24718026)

Authors

Höland K, Boller D, Hagel C, Dolski S, Treszl A, Pardo OE, Cwiek P, Salm F, Leni Z, Shepherd PR, Styp-Rekowska B, Djonov V, von Bueren AO, Frei K, Arcaro A

Title

Targeting class IA PI3K isoforms selectively impairs cell growth, survival, and migration in glioblastoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
PloS one	9	4	2014	e94132	PLoS One

URL

Abstract Text

The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancer and plays a crucial role in glioblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K isoforms as a novel anti-tumor approach in glioblastoma. Consistent expression of the PI3K catalytic isoform PI3K p110α was detected in a panel of glioblastoma patient samples. In contrast, PI3K p110β expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110α/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p110α activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p110α or PI3K p110β also led to impaired anchorage-independent growth, a decreased migratory capacity of glioblastoma cells, and reduced the activation of the Akt/mTOR pathway. These effects were selective, because targeting of PI3K p110δ did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110α can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110α/p-S6.

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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 H1047Y	glioblastoma	sensitive	YM-024	Preclinical	Actionable	In a preclinical study, glioblastoma cell lines harboring PIK3CA H1047Y demonstrated increased sensitivity to YM-024 induced growth inhibition (PMID: 24718026).	24718026
PIK3CA over exp	glioblastoma	sensitive	YM-024	Preclinical	Actionable	In a preclinical study, YM-024 inhibited proliferation and anchorage-independent growth of glioblastoma cell lines with elevated Pik3ca protein level in culture (PMID: 24718026).	24718026
PIK3CA V344G	glioblastoma	no benefit	YM-024	Preclinical	Actionable	In a preclinical study, YM-024 did not inhibit proliferation of glioblastoma cell lines harboring PIK3CA V344G in culture (PMID: 24718026).	24718026