Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy [Endocrinology. 2012] - PubMed - NCBI
Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy.
Abstract
More
than 90% of ovarian cancers have been thought to arise from epithelial
cells that cover the ovarian surface or, more frequently, line
subserosal cysts. Recent studies suggest that histologically similar
cancers can arise from the fimbriae of Fallopian tubes and from deposits
of endometriosis. Different histotypes are observed that resemble
epithelial cells from the normal Fallopian tube (serous), endometrium
(endometrioid), cervical glands (mucinous), and vaginal rests (clear
cell) and that share expression of relevant HOX genes which drive normal
gynecological differentiation. Two groups of epithelial ovarian cancers
have been distinguished: type I low-grade cancers that present in early
stage, grow slowly, and resist conventional chemotherapy but may
respond to hormonal manipulation; and type II high-grade cancers that
are generally diagnosed in advanced stage and grow aggressively but
respond to chemotherapy. Type I cancers have wild-type p53 and BRCA1/2,
but have frequent mutations of Ras and Raf as well as expression of IGFR
and activation of the phosphatidylinositol-3-kinase (PI3K) pathway.
Virtually all type II cancers have mutations of p53, and almost half
have mutation or dysfunction of BRCA1/2, but other mutations are rare,
and oncogenesis appears to be driven by amplification of several
growth-regulatory genes that activate the Ras/MAPK and PI3K pathways.
Cytoreductive surgery and combination chemotherapy with platinum
compounds and taxanes have improved 5-yr survival, but less than 40% of
all stages can be cured. Novel therapies are being developed that target
high-grade serous cancer cells with PI3Kness or BRCAness as well as the
tumor vasculature. Both in silico and animal models are needed that
more closely resemble type I and type II cancers to facilitate the
identification of novel targets and to predict response to combinations
of new agents.
