Jessica Teh, PhD, a Post-doctoral research fellow in the Department of Cancer Biology, Sidney Kimmel Cancer Center at Thomas Jefferson University was recently awarded the 2016 AACR-Ocular Melanoma Foundation Fellowship for her submission on, Utility of CDK4/6 inhibitors in uveal melanoma.
AACR based their decision on the relevance of her application to the mission of both AACR and a previous grant awarded from Outrun the Sun, with a belief that her project will have significant impact, and in recognition of her potential as a future leader in the ocular/uveal melanoma field. In December, Jessica received one of three scholar awards from Outrun the Sun, Inc., (www.outrunthesun.org) a nonprofit organization supporting skin cancer education and melanoma research.
Here is a complete project summary
Uveal melanoma is the most common intraocular malignant tumor in adults. It represents a rare subset of melanoma for which there is an important need for mechanistic understanding of the disease and for translational studies to provide the pre-clinical basis for new therapeutic strategies. After treatment of the primary tumor, 50% of uveal melanoma patients will develop macro-metastases without recurrence at the primary site. Currently, there are no FDA-approved targeted inhibitor treatments for metastatic uveal melanoma highlighting an important unmet need. MEK-ERK1/2 signaling is activated frequently in uveal melanoma due to driver mutations in either GNAQ or GNA11. While MEK inhibitors are FDA-approved in cutaneous melanoma, they provide a 14% response rate and modestly improve progression-free survival in uveal melanoma.
This proposal aims to utilize an in vivo reporter model to monitor the effects of the combination of MEK and CDK4/6 inhibitors and to identify optimal dosing schemes for this combination. Additionally, we will determine effect of BAP1 status in the modulation of response to the combination. In our studies, we will utilize new metastatic uveal melanoma cell lines, a new in vivo metastatic colonization model, and uveal melanoma patient samples from clinical trials. Ultimately through our experiments, we expect to provide the pre-clinical basis for targeted inhibitor combinations in late-stage uveal melanoma.