A gene expression profile test for the differential diagnosis of ovarian versus endometrial cancers.
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ABSTRACT:
SUBMITTER: Lal A
PROVIDER: S-EPMC3326651 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
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A gene expression profile test for the differential diagnosis of ovarian versus endometrial cancers.
Lal Anita A Panos Rebecca R Marjanovic Mira M Walker Michael M Fuentes Eloisa E Kapp Daniel S DS Henner W David WD Buturovic Ljubomir J LJ Halks-Miller Meredith M
Oncotarget 20120201 2
We have developed a gene expression profile test (Pathwork Tissue of Origin Endometrial Test) that distinguishes primary epithelial ovarian and endometrial cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 316-gene classification model. The test was validated in a blinded study using a pre-specified algorithm and microarray files for 75 metastatic, poorly differentiated or undifferentiated specimens with a known ovarian or endometrial cancer diagnosis. Measures of test perfor ...[more]
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Project description:Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4). To overcome these resistances, a new type of therapy has emerged named targeted therapy. The principle of targeted therapy is simple, taking advantage of changes acquired in malignant cancer cells (receptors, proteins, mechanisms) by using compounds specifically targeting these, thus limiting their action on healthy cells. Targeted therapies are emerging and many clinical trials targeting these pathways, frequently involved in chemoresistance, have been tested on gynecological cancers. Despite some targets being less efficient than expected as mono-therapies, the combination of compounds seems to be the promising avenue. For instance, we demonstrate using ChIP-seq analysis that estrogen downregulate tumor suppressor Par-4 in hormone-dependent cells by directly binding to its DNA regulatory elements and inhibiting estrogen signaling could reinstate Par-4 apoptosis-inducing abilities. This review will focus on the chemoresistance mechanisms and the clinical trials of targeted therapies associated with these, specifically for endometrial and ovarian cancers.
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