By inhibiting a protein that guides other proteins to fold into stable shapes, Fox Chase researchers have found a way to slow the growth of ovarian tumors. Molecular biologists Erica Golemis and Denise Connolly, together with medical oncologist Lainie Martin and colleagues, discovered that inhibiting heat shock protein 90 (HSP90) significantly depressed tumor growth and caused tumor cell death while showing no evidence of detrimental side effects. It also made cancerous cells more sensitive to standard chemotherapy agents such as cisplatin and paclitaxel.
“Ovarian cancer disseminates widely throughout the abdominal cavity and adheres to the colon and other vital organs. That’s what really causes mortality,” says Connolly. “Being able to identify therapeutic targets that actively inhibit the process of metastasis should be beneficial to these patients.”
The work that led to the discovery at Fox Chase was part of the National Cancer Institute’s Specialized Programs of Research Excellence in ovarian cancer. A Phase I/II clinical trial at Fox Chase is now testing the safety and efficacy of the HSP90 inhibitor ganetespib in combination with paclitaxel.
A different team of researchers, led by Golemis, found a potential benefit for treating another condition—autosomal dominant polycystic kidney disease (ADPKD). Their research showed that inhibiting HSP90 slowed the onset of cyst formation and improved kidney function in mice primed to develop a disease comparable to the human form of ADPKD.