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Gene | PIK3CA |
Variant | P449T |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | PIK3CA P449T lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). P449T results in increased Pik3ca kinase activity in cell culture (PMID: 20530683), and therefore, is predicted to lead to a gain of Pik3ca protein function. |
Associated Drug Resistance | |
Category Variants Paths |
PIK3CA mutant PIK3CA act mut PIK3CA P449T PIK3CA mutant PIK3CA exon8 PIK3CA P449T |
Transcript | NM_006218.4 |
gDNA | chr3:g.179210279C>A |
cDNA | c.1345C>A |
Protein | p.P449T |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_006713658.4 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
NM_006218.4 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
NM_006218.3 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
XM_006713658 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
XM_011512894.2 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
XM_006713658.5 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
NM_006218 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
XM_011512894 | chr3:g.179210279C>A | c.1345C>A | p.P449T | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E PIK3CA P449T | colorectal cancer | resistant | Cetuximab | Preclinical | Actionable | In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture (PMID: 25838391). | 25838391 |
BRAF V600E PIK3CA P449T | colorectal cancer | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). | 25838391 |
BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | Cetuximab + Regorafenib | Preclinical | Actionable | In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture (PMID: 25838391). | 25838391 |
BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | Everolimus + Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | Pimasertib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
BRAF V600E PIK3CA P449T TP53 R273H | colorectal cancer | sensitive | PD-0325901 + Sapanisertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and growth of colorectal cancer cells harboring BRAF V600E, PIK3CA P449T, and TP53 R273H in culture and in cell line xenograft models, but did not have synergistic effect on apoptosis (PMID: 26272063). | 26272063 |