Melanoma Molecular Disease- subtypes, including drugs, trials, and publications]

http://therapy.collabrx.com/melanoma/disease_model A Melanoma Molecular Disease Model Smruti J Vidwans(1), Keith T Flaherty(2), David E Fisher(3), Jay M Tenenbaum(1), Michael D Travers(1,5) and Jeff Shrager(4,1). (1) CollabRx Inc.

http://therapy.collabrx.com/melanoma/disease_model A Melanoma Molecular Disease Model Smruti J Vidwans(1), Keith T Flaherty(2), David E Fisher(3), Jay M Tenenbaum(1), Michael D Travers(1,5) and Jeff Shrager(4,1). (1) CollabRx Inc. Palo Alto CA 94301, USA (2) Department of Dermatology, Cutaneous Biology Research Center, and Melanoma Program, Massachusetts General Hospital, Boston, MA 021114, USA, (3) Massachusetts General Hospital Cancer Center, Boston, MA 02114, (4) Symbolic Systems Program (Consulting) and Stanford University CA 94301 USA,(5) Current address: SRI International, Artificial Intelligence Department, Menlo Park CA 94025. Melanoma Chief Editors: David Fisher, MD, PhD, Keith Flaherty, MD Melanoma Area Editors: Marcus W. Bosenberg, MD, PhD, Jeffrey E. Gershenwald, MD, Meenhard Herlyn, DVM, DSc, Harriet Kluger, MD, Glenn Merlino, PhD, Katherine L. Nathanson, MD, David Polsky, MD, PhD, Victor Prieto, MD, PhD, FACP, Antoni Ribas, MD, Lynn M. Schuchter, MD Editor in Chief: George D Lundberg, MD Acknowledgements: ''We thank Prof. Boris Bastian and Prof. Stephen Hodi for overall guidance and for pointing us to key pathways and genetic tests and Dr. Gavin Gordon for his thoughtful comments and proof-reading of this document.'' Abstract Melanoma subtypes are defined based on the status of key melanoma genes, pathways, and their combinations. Each subtype is defined by one key oncogene/tumor suppressor (such as BRAF for subtypes 1.1 to 1.4 and c-KIT for subtype 2.1) either by itself or in combination with others that play a supportive role (such as PTEN, AKT and CDK4 in the case of subtypes 1.2, 1.3 and 1.4). The subtype table below is generally organized by order of importance of associated oncogene/tumor suppressor, prevalence and potential for therapeutic intervention. Some of the oncogenes that define subtypes are capable of serving as the dominant oncogene and putative point of intervention for therapy, whereas others play a supportive role and typically co-exist with the mutations outlined in the first table. There are, of course, melanomas that do not fit into the currently defined subtypes, as well as types that do fit into an established subtype but do not respond as predicted. This may necessitate splitting of that subtype. Click here to read the peer-reviewed Melanoma Model paper in PLoS One: Vidwans SJ, Flaherty KT, Fisher DE, Tenenbaum JM, Travers MD, et al. (2011) A Melanoma Molecular Disease Model. PLoS ONE 6(3): e18257. doi:10.1371/journal.pone.0018257 Table of contents: [click on a section below to read details about that subtype, including drugs, trials, and publications] Section (subtype) Description Immuno Treatable Disease Immuno Treatable Disease http://therapy.collabrx.com/melanoma/subtype/Immuno_Treatable_Disease Subtype 1.1 Aberrations of the MAPK pathway http://therapy.collabrx.com/melanoma/subtype/Subtype_1.1 Subtype 2.1 Aberrations of the c-KIT pathway http://therapy.collabrx.com/melanoma/subtype/Subtype_2.1 Subtype 3.1 Aberrations of the GNAQ/GNA11 pathway http://therapy.collabrx.com/melanoma/subtype/Subtype_3.1 Subtype 3.2 Aberrations of the GNAQ/GNA11 pathway http://therapy.collabrx.com/melanoma/subtype/Subtype_4.1 Subtype 4.1 Aberrations of the NRAS pathway http://therapy.collabrx.com/melanoma/subtype/Subtype_4.1 Zelboraf Refractory Aberrations of the MAPK pathway and/or AKT/PI3K pathway http://therapy.collabrx.com/melanoma/subtype/Zelboraf_Refractory Most recent revision released on RELEASE-TTF-2012-12-13