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.

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 .