Our findings indicate that the adverse prognosis associated with TP53 and PIK3CA mutations in human cancers can be functionally replicated in mouse models of type I→type II OvCA progression.
We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC.
Recently, it has been reported that somatic mutations within the PI3K catalytic subunit, PIK3CA, are common (25-40%) among colorectal, gastric, breast, ovarian cancers, and high-grade brain tumors.
One patient exhibited mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other 4 exhibited concordant mutations.
We also found that an activating (E545K) Pik3ca mutation, unlike Pten inactivation or Pik3caH1047R mutation, cannot cooperate with Arid1a loss to promote ovarian cancer development in the mouse.
Interaction between PIK3CArs3976507 and rs6443626 loci, and factors such as BMI, number of liveborn, tobacco, alcohol, and family history of ovarian cancer are associated with ovarian cancer risk.
Although many tumors presented a single lesion (28/93, of which 23 overexpressed PIK3CA, 1 overexpressed AKT and 4 had lost PTEN), many OC (35/93) presented multiple alterations within the PI3K pathway.
Sequence mutations and gene amplifications lead to activation of the PIK3CA-AKT2 signaling pathway and have been reported in several types of neoplasms including ovarian cancer.
Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer.
Our results indicate that FAK inhibition can suppress ovarian cancer cells migration and invasion through inhibiting downstream signaling (PI3K/AKT), which might be a therapeutic target or biomarker for ovarian cancer.
The current results highlight the role of miR‑381‑mediated regulation of PIK3CA in the development and progression of ovarian cancer and suggest that restoration of miR‑381 to normal levels in ovarian cancer cells may constitute a therapeutic strategy for patients.
High prevalence of genetic alterations in PI3K/AKT pathway in a Middle Eastern ovarian carcinoma provides genetic evidence supporting the notion that dysregulated PI3K/AKT pathways play an important role in the pathogenesis of ovarian cancers.
Here, we show that dual inhibition of PI3K/mTOR in ovarian cancer-spheroids leads to death of inner matrix-deprived cells, whereas matrix-attached cells are resistant.
Activation of the phosphatidylinositol 3' kinase (PI3K) pathway occurs in a significant fraction of both types of ovarian cancer, driven predominantly by mutations in type I and amplification in type II.