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| 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. | ||||||||||||
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| 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. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 |
| 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 |