NEW GAMMA-SECRETASE INHIBITOR (RO4929097) TARGETING NOTCH SIGNALING IN MELANOMA

摘要

The incidence of melanoma has increased 3-7% per year, and is now approaching 30 per 100,000 individuals. This rate is faster than any other cancer, and is predicted to double every 10-20 years [1]. Surgery can be curative in Stage I, II, or III disease, but 75% of patients with deep primary lesions will develop extensive recurrence or distant metastases (Stage IV disease). To date, no curative treatment exists for Stage IV melanoma and these patients have a median overall survival of only 7 months [2]. A subset of patients can be salvaged with surgical resection of metastatic sites, but no adjuvant therapy has further improved the outcome [3]. The only FDA approved adjuvant therapy for Stage IV melanoma is alpha-interferon. Several trials have demonstrated an increase in relapse-free survival; however, toxicity is high and overall survival remains controversial. Several reports have demonstrated a role for aberrant Notch signaling in melanoma genesis or progression, prompting us to explore if targeting this pathway is a valid therapeutic approach against melanoma.