All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo<i>.</i> The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and <sup>V600E</sup>BRAF inhibition.
Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors.
Mutations of components of the mitogen-activated protein kinase pathway, mainly BRAF, are common in serous ovarian borderline tumors, whereas high-grade serous ovarian carcinomas rarely show this feature.
Seven patients (30%) with PIK3CA mutations had coexisting MAPK pathway (KRAS, NRAS, BRAF) mutations (ovarian cancer, n = 5; endometrial cancer, n = 2), and two of these patients (ovarian cancer) achieved a response.
We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005).
Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer.
The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggests that low-grade and high-grade ovarian serous carcinomas develop through independent pathways.