Somatic mutations in PIK3CA have been found in 10--30% of colorectal cancers. KRAS, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies in metastatic colorectal cancer. Recent 'molecular pathological epidemiology' (MPE) research has shown that aspirin use may be associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation may be a molecular biomarker that predicts response to aspirin therapy. The R88Q mutation falls within the ABD domain of the p110a catalytic subunit and has been shown to result in gain-of-function in vitro. PIK3CA may be a target of directed therapy in some clinical settings.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in various tumor types including up to 36% and 11% of hepatocellular carcinoma and gastric cancer, respectively. They are detected less frequently in cholangiocarcinoma (~6%) and pancreatic adenocarcinoma (~4%). The predictive and prognostic significance of PIK3CA mutations in adenocarcinoma of the small intestine is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exons 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in various tumor types including up to 36% and 11% of hepatocellular carcinoma and gastric cancer, respectively. They are detected less frequently in cholangiocarcinoma (~6%) and pancreatic adenocarcinoma (~4%). The predictive and prognostic significance of PIK3CA mutations is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

The catalytic subunit (p110a) of phosphatidylinositol-3-kinase (PI3K) is encoded by the PIK3CA gene and acts to activate several signaling cascades, including the well-characterized AKT-mTOR pathway that promotes cell survival, proliferation, growth and motility. PIK3CA is among the most commonly mutated genes in cancer and aberrant activation of PI3K is a transforming event. Somatic mutations in PIK3CA are seen in approximately 2% of papillary thyroid carcinoma, poorly differentiated carcinoma, anaplastic carcinoma. Somatic mutations of PIK3CA have been described particularly in advanced and dedifferentiating thyroid tumors. Their prevalence varies from 16 to 23% in anaplastic thyroid carcinomas. They are less frequent in papillary and follicular thyroid carcinomas and the prevalence in medullary thyroid carcinomas remains unknown. Although inhibitors of the PI3K/AKT/mTOR pathway have shown efficacy against thyroid cancer in pre-clinical models, their success in clinical trials remains to be determined.

Somatic mutations in PIK3CA have been found in 10-30% of colorectal cancers. According to some reports, co-occurrence of both exon 9 and exon 20 PIK3CA mutations, when present, may be associated with a poor prognosis. Recent 'molecular pathological epidemiology' (MPE) research has shown that aspirin use is associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation may be a molecular biomarker that predicts response to aspirin therapy. PIK3CA may also be a target of directed therapy in some clinical settings.

Somatic mutations in PIK3CA are seen in approximately 2% of papillary thyroid carcinoma, poorly differentiated carcinoma, anaplastic carcinoma. Somatic mutations of PIK3CA have been described particularly in advanced and dedifferentiating thyroid tumors. Their prevalence varies from 16 to 23% in anaplastic thyroid carcinomas. They are less frequent in papillary and follicular thyroid carcinomas and the prevalence in medullary thyroid carcinomas remains unknown. Although inhibitors of the PI3K/AKT/mTOR pathway have shown efficacy against thyroid cancer in pre-clinical models, their success in clinical trials remains to be determined.

PIK3CA mutations have been identified in pediatric and adult gliomas including: anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme, rosette forming glioneuronal tumors and medulloblastomas. PIK3CA mutations provide a mechanism for disrupting the PI3K/Akt pathway.

Somatic mutations in PIK3CA have been found in 1–3% of NSCLC. These mutations typically occur within specific hotspot regions. PIK3CA mutations appear to be more common in squamous cell histology compared to adenocarcinoma and can occur with or without a history of smoking. PIK3CA mutations can co-occur with EGFR mutations and PIK3CA mutations have been detected in a small percentage (approximately 5%) of EGFR-mutated lung cancers with acquired resistance to EGFR TKI therapy.

Somatic mutations in PIK3CA have been found in 10-30% of colorectal cancers. KRAS, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies in metastatic colorectal cancer. According to some reports, co-occurrence of both exon 9 and exon 20 PIK3CA mutations, when present, may be associated with a poor prognosis. Recent 'molecular pathological epidemiology' (MPE) research has shown that aspirin use may be associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation may be a molecular biomarker that predicts response to aspirin therapy. PIK3CA may also be a target of directed therapy in some clinical settings.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. PIK3CA mutations are present in ~5% of cutaneous melanomas. PIK3CA M1043I is a known oncogenic hotspot mutation. M1043I confers a gain of function on the protein as indicated by in increased activation of downstream signaling and and transformation in cell culture. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

The catalytic subunit (p110a) of phosphatidylinositol-3-kinase (PI3K) is encoded by the PIK3CA gene and acts to activate several signaling cascades, including the well-characterized AKT-mTOR pathway that promotes cell survival, proliferation, growth and motility. PIK3CA is among the most commonly mutated genes in cancer and aberrant activation of PI3K is a transforming event. Somatic mutations in PIK3CA have been found in 1--3% of NSCLC and genetic alteration in PIK3CA have been identified in 7% of lung adenocarcinomas. These mutations typically occur within specific hotspot regions. PIK3CA mutations appear to be more common in squamous cell histology compared to adenocarcinoma and can occur with or without a history of smoking. PIK3CA mutations can co-occur with EGFR mutations and PIK3CA mutations have been detected in a small percentage (approximately 5%) of EGFR-mutated lung cancers with acquired resistance to EGFR TKI therapy. The PIK3CA H1047R mutation is known to be oncogenic.

The catalytic subunit of phosphatidylinositol-3-kinase (PI3K) is encoded by the PIK3CA gene. PIK3CA is among the most commonly mutated genes in cancer and aberrant activation of PI3K is a transforming event. PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in various tumor types including up to 36% and 11% of hepatocellular carcinoma and gastric cancer, respectively. They are detected less frequently in cholangiocarcinoma (~6%) and pancreatic adenocarcinoma (~4%). The predictive and prognostic significance of PIK3CA mutations is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors. The PIK3CA N1044K mutation is known to be oncogenic.

PIK3CA is the the p110 catalytic subunit-alpha of phosphatidylinositol 3 kinase. Activating mutations of PIK3CA occur in various types. PIK3CA mutations have been reported in approximately 8% of cases of diffuse large B cell lymphoma and are typically mutually exclusive of PTEN loss in that tumor type. PIK3CA mutations are very rare in chronic lymphocytic leukemia and believed to be absent in acute myeloid leukemia and myelodysplastic syndromes. PIK3CA mutations are potentially targetable in some settings and pathway inhibitors are currently under investigation .

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways.The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with 80% of the identified mutations found within three hotspot: E542K, E545K, and H1047R. PIK3CA mutations are often found in hormone receptor positive breast cancer and have been associated with resistance to anti-EGFR therapy in some studies but not in others.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways.The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains). Activating mutations in PIK3CA are found are found in a wide variety of human cancers including 27% urothelial bladder cancers, with a higher prevalence in low grade tumors. Up to 13.6% of renal pelvic urothelial carcinomas also harbor activating somatic mutations in PIK3CA gene. The role of PIK3CA mutations as prognosticators of outcome or predictors of therapeutic response awaits further evaluation.

PIK3CA mutations have been identified in pediatric and adult gliomas including: anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme, rosette forming glioneuronal tumors and medulloblastomas. Although PIK3CA mutations are reported in medulloblastoma, their role in tumorigenesis remains controversial. According to some preclinical studies, mutations in PIK3CA likely activate the AKT pathway to progress, rather than initiate, WNT-medulloblastoma. PIK3CA mutations are potentially targetable in some settings and pathway inhibitors are currently under investigation.

The catalytic subunit (p110a) of phosphatidylinositol-3-kinase (PI3K) is encoded by the PIK3CA gene and acts to activate several signaling cascades, including the well-characterized AKT-mTOR pathway that promotes cell survival, proliferation, growth and motility. PIK3CA is among the most commonly mutated genes in cancer and aberrant activation of PI3K is a transforming event. Somatic mutations in PIK3CA have been found in 1--3% of NSCLC and genetic alteration in PIK3CA have been identified in 7% of lung adenocarcinomas. These mutations typically occur within specific hotspot regions. PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in 8-21% and 20-33% of head/neck and anal squamous cell carcinoma, respectively. PIK3CA mutations, especially ones involving the helical domain, in these types of squamous cell carcinoma are highly associated with HPV. The predictive and prognostic significance of PIK3CA mutations in squamous cell carcinoma is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in various tumor types including up to 36% and 11% of hepatocellular carcinoma and gastric cancer, respectively. They are detected less frequently in cholangiocarcinoma (~6%) and pancreatic adenocarcinoma (~4%). The predictive and prognostic significance of PIK3CA mutations is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains). Activating mutations in PIK3CA are found in a wide variety of human cancers including up to 4% of prostate cancers. The role of PIK3CA mutations as prognosticators of outcome or predictors of therapeutic response awaits further evaluation. Clinical trials are available for patients with PIK3CA mutated tumors.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains). Activating mutations in PIK3CA are found in a wide variety of human cancers including up to 5% of renal cell carcinomas. The role of PIK3CA mutations as prognosticators of outcome or predictors of therapeutic response awaits further evaluation. Clinical trials are available for patients with PIK3CA mutated tumors.

This gene is a known cancer gene.

This gene is a known cancer gene.

AKT1 mutations have been reported in a variety of tumor types such as endometrial, lung, breast, colorectal, ovarian, and prostate cancers. The mutations are mutually exclusive from PIK3CA mutations. Increased expression and activation of AKT1 observed in many cancers is caused by a variety of different mechanisms including genomic alterations of AKT1, PIK3CA, PTEN, RAS family members, or growth factor receptors. Gain-of-function alterations of AKT1 can lead to neoplastic transformation in model systems, and is a potential target for therapeutic strategies. The E17K variant is by far the most frequent AKT1 mutation reported, implicating it as an important tumor promoting event.

AKT1 mutations have been reported in a variety of tumor types such as endometrial, lung, breast, colorectal, ovarian, urothelial and prostate cancers. The mutations are mutually exclusive from PIK3CA mutations. Increased expression and activation of AKT1 observed in many cancers is caused by a variety of different mechanisms including genomic alterations of AKT1, PIK3CA, PTEN, RAS family members, or growth factor receptors. Gain-of-function alterations of AKT1 can lead to neoplastic transformation in model systems, and is a potential target for therapeutic strategies. The E17K variant is by far the most frequent AKT1 mutation reported, implicating it as an important tumor promoting event.

PTEN mutations occur in 5-14% of colorectal cancers. PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. PTEN loss of expression is observed with KRAS, BRAF, and PIK3CA mutations. In retrospective studies, PTEN loss is associated with decreased sensitivity of colorectal cancer tumors to anti-EGFR antibodies. PTEN loss is associated with lack of benefit of the anti-EGFR antibody, cetuximab.

FGFR3 has been found to be mutated in up to 64% of cases of bladder cancer; FGFR3 mutations tend to be exclusive of RAS mutations ,TP53 overexpression, TP53 mutation, but not PIK3CA mutations. However, subsets of cases with co-mutations have been described. FGFR3 mutations (including Y373C) are believed to lead to constitutive activation of the receptor and activation of the RAS-MAPK pathway. FGFR3 mutations are often seen in non-muscle invasive bladder cancers and tend to correlate with low stage and grade; however FGFR3 mutations have also been described in muscle-invasive bladder cancer. Targeted therapies with FGFR3 inhibitors have been explored in patients with bladder cancer.

Balversa (erdafitinib) has been FDA approved for treatment of urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations. FGFR3 is a receptor tyrosine kinase in the RAS-MAPK and PI3K-AKT pathways. FGFR3 has been found to be mutated in up to 64% of cases of bladder cancer and 40% of upper urothelial tract (ureter and renal pelvis) urothelial carcinomas. FGFR3 mutations tend to be exclusive of RAS mutations ,TP53 overexpression, TP53 mutation, but not PIK3CA mutations. However, subsets of cases with co-mutations have been described. Gain of function FGFR3 mutations (including FGFR3 R248C and FGFR3 S249C) are believed to lead to constitutive activation of the receptor and activation of the RAS-MAPK pathway. FGFR3 mutations are often seen in non-muscle invasive bladder cancers and tend to correlate with low stage and grade; however, FGFR3 mutations have also been described in muscle-invasive bladder cancer.