Identifying Therapeutics for Platinum-Resistant Ovarian Cancer by Next-Generation Mechanotyping
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2018
- Accession Number
- AD1095447
Entities
People
- Amy Rowat
Organizations
- University of California, Los Angeles