Identifying Therapeutics for Platinum-Resistant Ovarian Cancer by Next Generation Mechanotyping
Technical Report,15 Aug 2016,14 Aug 2017
University of California, Los Angeles Los Angeles United States
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Treatment of high grade serous ovarian is initially effective in reducing the growth tumors, but cancer recurs in over 80 of ovarian cancer patients because cells become resistant to common, platinum-resistant chemotherapy drugs. There is a critical need for new drugs that target platinum-resistant cancer cells. We recently discovered that platinum-resistant ovarian cancer cells are more deformable than their drug-sensitive counterparts. We hypothesized that we could identify novel compounds that selectively target drug-resistant ovarian cancer cells by screening cells against libraries of small molecules using the novel Parallel Microfiltration PMF screening technology that we recently invented. In this first funding period, we have successfully advanced and integrated the PMF technology into the Molecular Shared Screening Resource at UCLA, thereby establishing the first facility for mechanotype screening. We have designed and optimized conditions for the mechanotype screen. Our proof-of-concept screen of cisplatin-resistant ovarian cancer cells against the Library of Pharmacologically Active CompoundsLOPAC reveals several lead compounds. The pending studies will validate the effects of the lead compounds on cisplatin-resistant ovarian cancer cells, including cellular and molecular analyses.
- Medicine and Medical Research