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)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA163222-02
Application #
8736410
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
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
Romano, Gabriele; Chen, Pei-Ling; Song, Ping et al. (2018) A Preexisting Rare PIK3CAE545K Subpopulation Confers Clinical Resistance to MEK plus CDK4/6 Inhibition in NRAS Melanoma and Is Dependent on S6K1 Signaling. Cancer Discov 8:556-567
Wein, Marc N; Foretz, Marc; Fisher, David E et al. (2018) Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential. Trends Endocrinol Metab 29:723-735
Levy, Carmit; Golan, Tamar; Fisher, David E (2018) miRNA-211 stops the clock. Noncoding RNA Investig 2:
Eliades, Philip; Abraham, Brian J; Ji, Zhenyu et al. (2018) High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma. J Invest Dermatol 138:1582-1590
Nguyen, Nhu T; Fisher, David E (2018) MITF and UV responses in skin: From pigmentation to addiction. Pigment Cell Melanoma Res :
Kapp, Friedrich G; Perlin, Julie R; Hagedorn, Elliott J et al. (2018) Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 558:445-448
Byrne, Elizabeth H; Fisher, David E (2017) Immune and molecular correlates in melanoma treated with immune checkpoint blockade. Cancer 123:2143-2153
Lin, William M; Fisher, David E (2017) Signaling and Immune Regulation in Melanoma Development and Responses to Therapy. Annu Rev Pathol 12:75-102
Kawakami, Akinori; Fisher, David E (2017) The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology. Lab Invest 97:649-656
Reuben, Alexandre; Spencer, Christine N; Prieto, Peter A et al. (2017) Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med 2:

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