Identifying Therapeutics for Platinum-Resistant Ovarian Cancer by Next-Generation Mechanotyping
Technical Report,15 Aug 2017,14 Aug 2018
University of California Los Angeles United States
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Treatment of high grade serous ovarian is initially effective in reducing the growth of tumors, but cancer recurs in over 80 percent 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 second funding period, we have successfully conducted the first mechanotype screen, identifying top hits from the Library of Pharmacologically Active Compounds LOPAC that cause cisplatin-resistant ovarian cancer cells to be less deformable. Orthogonal studies across multiple human ovarian cancer cell lines reveal that top hits consistently cause ovarian cancer cells to be less invasive, suggesting that mechanotype screening may provide a surrogate to identify compounds that complement existing therapeutic strategies.
- Medicine and Medical Research
- Anatomy and Physiology