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.''
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
|Immuno Treatable Disease||Immuno Treatable Disease|
|NRAS Zelboraf Refractory||Aberrations of the MAPK pathway and NRAS pathway|
|Subtype 1.1||Aberrations of the MAPK pathway|
|Subtype 2.1||Aberrations of the c-KIT pathway|
|Subtype 3.1||Aberrations of the GNAQ/GNA11 pathway|
|Subtype 3.2||Aberrations of the GNAQ/GNA11 pathway|
|Subtype 4.1||Aberrations of the NRAS pathway|
|Zelboraf Refractory||Aberrations of the MAPK pathway and/or AKT/PI3K pathway|
Dear Therapy Finder® User:
During the past two years we have witnessed an unprecedented upswing in research activity leading to the identification of increasing numbers of actionable biomarkers and several effective targeted treatments. To accommodate this dramatic increase in the number of relevant biomarkers, their interactions, and other patient attributes, we are developing a new application design, one that will be both easier to use and more relevant to practicing physicians and patients. This new system will unify many of the best features and key learnings from the Therapy Finders with those from our Genomic Variant Annotation™ (GVA) reporting system.
Until we complete the redesign of our Therapy Finders or offer substitute decision-support products, we are suspending the updating of the Therapy Finders appearing on the CollabRx website and other sites.
If you click through and decide to use the Colon Cancer, Lung Cancer, Melanoma or Metastatic Breast Cancer Therapy Finders, please do so with caution, as some of the data have not been updated since October 15, 2014.
July 6, 2015