Novel drugs targeting metastatic cancers
Inventors: Bruce Zetter, Courtney Barrows, Ivy Chung
Keywords: Drug Screening
Dr. Zetter and colleagues developed a four-step screen that relies on differential cytotoxicity of drugs for highly metastatic cells to identify novel therapeutic agents for late-stage cancer. From a library of 1120 non-toxic FDA-approved drugs, benzimidazoles were identified as a class of compounds that are preferentially active against highly metastatic prostate tumor cells and exhibit minimal cell kill in normal cells was selected. These drugs showed synergistic anti-tumor activity with paclitaxel, displayed cytotoxic activity in paclitaxel-resistant prostate cancer cells and prolonged survival of animals with disseminated prostate cancer by an average of 51% when administered after lung metastatic colonies were established. Dr. Zetter and colleagues also designed alternative formulations of these drugs to enhance further the anti-metastatic effect.
This project is a recipient of a CHB Technology Development Fund award in 2010.
This class of drugs could be clinically useful therapeutic agents for metastatic prostate cancer. There are approximatively 200,000 new cases of prostate cancer and an estimated 30,000 deaths. A quarter of patients who have undergone radical prostatectomy are likely to develop metastasis within 10 years. Androgen ablation is an effective treatment for these advanced stages, but the disease almost inevitably progresses to a castrate-resistant state for which taxanes and palliative care are the only two options. Almost all of these patients will eventually develop taxane resitance and their prognosis is very poor.
• Answers unmet medical need: no approved therapy for established metastases, may be treatment for advanced castrate-resistant prostate cancers for which there is limited treatment options
• Potent activity in treating existing metastasis: prolongs survival in mice when dosing starts after metastasis are established; increased life span with selected drugs twice as long as paclitaxel; active in paclitaxel-resistant prostate cancer cells
• Novel formulation: allows for systemic delivery and increased bioavailability which results in optimized cytotoxicity; new IP filed; original drug formulations are FDA-approved and demonstrate little toxicity
• Potential expansion to other cancers: observed in vitro cytotoxicity in human osteosarcoma, fibrosarcoma, uterine sarcoma, as well as pancreatic, renal, breast and lung cancers
• Powerful screening platform: can be used to identify drugs for other metastatic cancers; characterization of other hits from the metastatic prostate cancer screen is underway
Exclusive license and/or sponsored research available
Key Publications: Published PCT application: WO 2010/135534
IPStatus: Pat. Pend.