Biomarker: phosphatidylinositol 3'-kinase pathway alteration

Histology type: endometrial carcinoma

Country: China

Region: Beijing

Study type: retrospective study

Followed up time : 79 months (range, 1-129 months)

Subgroup 1 name : mutation

Subgroup 1 number: 29

Subgroup 2 name: wide

Subgroup 2 number: 53

Description: Our findings suggest that phosphatidylinositol 3'-kinase pathway alteration might have a favorable prognostic impact on endometrial cancers in Chinese women. Furthermore, the function of the phosphatidylinositol 3'-kinase pathway might be affected by estrogen receptor status.

Sample type : tissue

Statictics: Median;Range

Cohort age: 55;32-79

Description: The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in human cancer and represents an attractive target for therapies based on small molecule inhibitors. PI3K isoforms play an essential role in the signal transduction events activated by cell surface receptors including receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). There are eight known PI3K isoforms in humans, which have been subdivided into three classes (I-III). Therefore PI3Ks show considerable diversity and it remains unclear which kinases in this family should be targeted in cancer. The class IA of PI3K comprises the p110α, p110β and p110δ isoforms, which associate with activated RTKs. In human cancer, recent reports have described activating mutations in the PIK3CA gene encoding p110α, and inactivating mutations in the phosphatase and tensin homologue (PTEN) gene, a tumour suppressor and antagonist of the PI3K pathway. The PIK3CA mutations described in cancer constitutively activate p110α and, when expressed in cells drive oncogenic transformation. Moreover, these mutations cause the constitutive activation of downstream signaling molecules such as Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K) that is commonly observed in cancer cells. In addition to p110α, the other isoforms of the PI3K family may also play a role in human cancer, although their individual functions remain to be precisely identified. In this review we will discuss the evidence implicating individual PI3K isoforms in human cancer and their potential as drug targets in this context.[PMC2652403]