Molecular disease model for melanoma

Published as a "dynamic" review paper by a panel of leading researchers and clinicians affiliated with the Cancer Commons initiative, the MDMM is maintained online, curated by the authors and continuously updated based on input from the melanoma community to reflect the latest scientific, clinical and technological advancements in cancer research and treatment. The MDMM is designed as an interface between the research and clinical communities where researchers can learn from clinical outcomes to refine molecular subtypes and clinicians can use the latest subtype information in treatment decisions. In this way, the online melanoma disease model becomes the core of an adaptive, rapid learning community that provides each patient with the best possible outcome while aggregating results over all patients to advance the standard of care.

The MDMM consists of a set of "actionable" molecular subtypes and proposed practice guidelines for treating each subtype: which therapies (approved or experimental) should be considered and which are contraindicated. A molecular subtype of melanoma is loosely defined as those tumors containing the same set of molecular (primarily genetic) defect(s) and their associated pathways. A subtype is deemed actionable if there is both a CLIA-approved assay to determine whether a given tumor fits that classification, and at least one FDA-approved or experimental targeted therapy with potential efficacy for that subtype.

Commented Dr. Keith Flaherty, Director of Developmental Therapeutics at Massachusetts General Hospital and co-chief editor of Cancer Commons Melanoma: "While earlier stages of melanoma can be successfully treated by surgical excision, advanced stages are uniquely refractory to standard chemotherapy. Recent developments in our understanding of the molecular drivers of this disease have led to a new generation of targeted therapies that are proving effective in patients whose tumors harbor certain genetic defects. Rather than treating melanoma as a single disease, it makes sense to stratify tumors into molecular subtypes and treat each with the most appropriate therapies."

The molecular disease model for melanoma is the first of many such models planned by Cancer Commons, the open science initiative for personalized oncology that was initially convened by CollabRx. Cancer Commons is creating a network of rapid learning communities where physicians, scientists, and patients collaborate to provide each patient with the best possible outcome by personalizing therapy based on the tumor's genomic subtype. CollabRx is developing web-based applications and services that facilitate this collaboration; the first of these, The Targeted Therapy Finder -- Melanoma, leverages the MDMM to find treatments targeted to a patient's specific molecular profile.

Funding: SJV, JMT, MDT and JS are or were employees of CollabRx, Inc. a for-profit corporation. They played intimate roles in the research and preparation of the manuscript.