| 摘要 |
<p>The invention provides: screening for ovarian cancer by detecting the presence of a loss-of-function-related genetic alteration in the PAPPA gene or its regulatory or promoter sequences in a sample obtained from the subject, wherein the presence of a genetic alteration is indicative of ovarian cancer; Methods for aiding the diagnosis of ovarian cancer by detecting the presence of a mitotic delay phenotype in a sample obtained from the patient and/or detecting the level of PAPPA and/or PAPPA functional activity, wherein identification of the mitotic delay phenotype, and/or the absence of functional PAPPA, or the presence of functional PAPPA at a reduced level compared to a control, is indicative of ovarian cancer; Prognostic methods for determining the risk of atypical proliferative epithelial lesions or tumours progressing to invasive ovarian cancer by identifying the proportion of mitotic cells in a patient sample that are in prophase or prometaphase; Therapeutic aspects of the invention enable the sensitisation of mitotically delayed ovarian cancer cells to anti-proliferative agents, preferably anti-mitotic agents, by restoring normal progression through mitosis. In this embodiment a first therapeutic agent is applied to release ovarian cancer cells from the mitotic block and a second therapeutic agent or therapy affecting proliferating cells is administered to kill the cycling cancer cells.</p> |
