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June 2, 2021

Dermatology Advances Into an Era of Precision Medicine

Author Affiliations
  • 1Department of Dermatology, Stanford University School of Medicine, Stanford, California
JAMA Dermatol. Published online June 2, 2021. doi:10.1001/jamadermatol.2021.0024

On August 17, 2011, after a decade characterized by a dearth of new therapies for advanced melanoma, vemurafenib was approved as the first targeted therapy for unresectable or metastatic melanoma.1 Vemurafenib was designed to target only BRAF V600E-positive melanomas, thereby increasing efficacy and reducing the off-target systemic toxic effects seen in prior melanoma treatments, such as high-dose interferon. This historic breakthrough marked a major milestone in precision oncology, the practice of selecting a treatment based on the genetics and molecular characteristics of an individual patient’s tumor, and opened the door to a new era of targeted therapy for dermatologic conditions.

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    1 Comment for this article
    Time to Step into The Future with Gene Expression Testing
    Binh Ngo, M.D. | Keck USC School of Medicine, Department of Dermatology
    Dermatology is slowly joining oncology in using gene expression profiles to motivate specific treatments. Certainly, visual recognition of characteristics on biopsy slides has always been the standard approach to classifying skin disease. Yet it is now clear that genetic expression adds significantly to prediction for development of skin cancers and for prognosis of evolution of cutaneous malignancy. This has been shown for melanoma and squamous cell cancer (1-6). It is certainly appropriate to integrate gene expression into standard management of skin cancer, particularly in families with historical susceptibility. The challenge has always been cost. Detailed economic analyses have guided third parties in making reimbursement decisions. At this time, coverage for gene expression testing is piecemeal and limited. Yet, the tragedy of COVID-19 has illustrated the massive economic costs of disease to society. The large outlays of Operation Warp Speed to develop vaccines have been miniscule compared to the massive global economic losses of the pandemic. The lessons learned from COVID-19 have been condensed in time, but should guide us in liberalizing support for new diagnostic, prognostic and therapeutic gene expression testing.

    1) Landi MT, Bishop DT, MacGregor S,et al. Genome-wide association meta-analyses combining multiple risk phenotypes provides insights into the genetic architecture of cutaneous melanoma susceptibility Nat Genet. 2020 May; 52(5): 494–504

    2) Garg M, Couturier DL, Nsengimana J, et al. Tumour gene expression signature in primary melanoma predicts long-term outcomes. Nat Commun. 2021; 12: 1137. Published online 2021 Feb 18
    3) Cirenajwis H, Ekedahl H, Lauss M, et al. Molecular stratification of metastatic melanoma using gene expression profiling : Prediction of survival outcome and benefit from molecular targeted therapy. Oncotarget. 2015 May 20; 6(14): 12297–12309

    4) Leachman SA, Mengden Koon S, Korcheva VB, et al. assessing genetic expression profiles in melanoma diagnosis. Dermatol Clin. 2017 Oct;35(4):537-544

    5) Rebeca T, Giselle P, Litchman GH, et al. Impact of gene expression profile testing on the management of squamous cell carcinoma by dermatologists. J Drugs Dermatol. 2019 ;18(10):980-984

    6) Wysong A, Newman JG,. Covington KR, et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. Journal of the American Academy of Dermatology 2021; 84(2): 361-369
    CONFLICT OF INTEREST: Dr. Ngo has been an investigator for Castle Biosciences and has been a speaker at educational sessions supported by that company