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| Gene | PIK3CA |
| Variant | E453K |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | PIK3CA E453K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453K results in increased phosphorylation of Akt and Mek1/2, enhanced cell survival, increased cell proliferation and migration, and is transforming in culture (PMID: 26627007, PMID: 29533785, PMID: 34779417). |
| Associated Drug Resistance | |
| Category Variants Paths |
PIK3CA mutant PIK3CA act mut PIK3CA E453K PIK3CA mutant PIK3CA exon8 PIK3CA E453K |
| Transcript | NM_006218.4 |
| gDNA | chr3:g.179210291G>A |
| cDNA | c.1357G>A |
| Protein | p.E453K |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_006218 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| XM_006713658.5 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| NM_006218.3 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| NM_006218.4 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| XM_006713658.4 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| XM_011512894.2 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| XM_006713658 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| XM_011512894 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PIK3CA E453K | breast cancer | resistant | Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cells expressing PIK3CA E453K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477). | 29636477 |
| PIK3CA E453K | lung squamous cell carcinoma | no benefit | Taselisib | Case Reports/Case Series | Actionable | In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in a patient harboring PIK3CA E453K (PMID: 31158500; NCT02785913). | 31158500 |
| PIK3CA E453K | breast cancer | decreased response | LY294002 | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line expressing PIK3CA E453K was less sensitive to LY294002 treatment compared to cells overexpressing wild-type PIK3CA or PIK3CA E418K in culture (PMID: 38909932). | 38909932 |