Core A - Melanoma Biobank The propagation of human cancer cells has been a vital part of cancer biology including the seminal discovery of BRAF mutations in melanoma. Historically, cancer lines have proven to be a powerful system for screening novel therapeutic compounds and for isolating molecular determinants of sensitivity to anti-cancer drugs. The main charge of Core A- the Melanoma Biobank (MBB)- is to establish a critical set of melanoma cell lines from patients who undergo treatment with selective Braf inhibitors or other novel agents. Vital derivatives from Core A, along with annotated specimens, will be available to the rest of the P01 for molecular verification and functional validation of target candidates which may emerge from the various screens.
The Specific Aims of Core A are (1) to provide a central source of melanoma cells obtained prior to initiation of selective Braf inhibitors (SBIs) and during relapse while undergoing treatment, (2) to provide mutational, copy number, expression and pathway actiyation profiles on cell lines and (3) to provide sensitivity data for selective BRAF inhibitors and other targeted therapies and to compare drug responses across various targeted agents and (4) to maintain a clinical database and tissue repository derived from patients on targeted therapy trials. This last Aim will leverage extant funding and will provide a critical piece of the correlative puzzle in the overall translational effort. By the end of the funded period, successful integration of all Projects and Cores within the POI will yield an unprecedented set of tissue specimens and vital cells adorned with meticulous clinical annotation and in-depth molecular profiling.

Public Health Relevance

The use of living cancer cells has been invaluable in our ability to identify new treatments and to test novel drugs. The mission of this Core facility is to maintain a bank of living melanoma cells for careful study and for future drug discovery. The overall goal of the Program Project is to better understand why patients continue to relapse from anti-Braf drugs.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01CA163222-02
Application #
8736410
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Roider, Elisabeth M; Fisher, David E (2014) The impact of MITF on melanoma development: news from bench and bedside. J Invest Dermatol 134:16-7
Konieczkowski, David J; Johannessen, Cory M; Abudayyeh, Omar et al. (2014) A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 4:816-27
Van Allen, Eliezer M; Wagle, Nikhil; Sucker, Antje et al. (2014) The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 4:94-109
Lo, Jennifer A; Fisher, David E (2014) The melanoma revolution: from UV carcinogenesis to a new era in therapeutics. Science 346:945-9
Wagle, Nikhil; Van Allen, Eliezer M; Treacy, Daniel J et al. (2014) MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov 4:61-8
Sullivan, Ryan J; Fisher, David E (2014) Understanding the biology of melanoma and therapeutic implications. Hematol Oncol Clin North Am 28:437-53
Pop, Marius S; Stransky, Nicolas; Garvie, Colin W et al. (2014) A small molecule that binds and inhibits the ETV1 transcription factor oncoprotein. Mol Cancer Ther 13:1492-502
Chen, Hongxiang; Weng, Qing Y; Fisher, David E (2014) UV signaling pathways within the skin. J Invest Dermatol 134:2080-5
Fell, Gillian L; Robinson, Kathleen C; Mao, Jianren et al. (2014) Skin ?-endorphin mediates addiction to UV light. Cell 157:1527-34
Hsiao, Jennifer J; Fisher, David E (2014) The roles of microphthalmia-associated transcription factor and pigmentation in melanoma. Arch Biochem Biophys 563:28-34

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