Kenneth Y Tsai

Guest Editor for the following articles:

Jun
2014
Vol. 33. No. 2

Current status and future directions of molecularly targeted therapies and immunotherapies for melanoma

David M Miller, MD | Hensin Tsao, MD | Keith T Flaherty, MD
Key molecular and immunological insights over the past decade have radically changed the face of therapy in melanoma. Whereas 5 years ago, treatment for advanced melanoma was restricted to the alkylating agent dacarbazine and the immunostimulants interleukin-2 and interferon-a-2b, today the therapeutic menu includes precise therapies that target key determinants in oncogenic pathways and immune checkpoints. In this chapter, we will review the current status and future directions of targeted therapies for melanoma directed at mitogen-activated pathways and immune checkpoints. Semin Cutan Med Surg 33:60-67 © 2014 Frontline Medical Communications
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Jun
2014
Vol. 33. No. 2

Gene therapies for inherited skin disorders

Alya Abdul-Wahab, BSc, MBBS, MRCP(UK) | John A McGrath, MD, FRCP, FMedSci | Waseem Qasim, MBBS, PhD, MRCPCH
Skin is an amenable organ for gene replacement and gene editing therapeutics. Its accessibility makes it wellsuited for direct topical gene delivery, grafting of genetically corrected cells, and monitoring of possible adverse events. Monogenic recessive disorders with a clinically severe or life-threatening phenotype provide the best candidate diseases for the introduction of a single normal copy of the gene into the target cell, usually keratinocytes. Preclinical studies have shown impressive results in terms of gene correction using both in vivo and ex vivo approaches. The clinical application of gene replacement or genomic editing as potential therapies for inherited skin disorders, however, has been held back by the inadequacy of delivery vectors and concerns from regulatory agencies regarding safety; thus translation to clinical trials has been slow. Over the past 15 years, cell culture and animal models have shown efficient gene correction techniques as preludes to treat inherited skin disorders such as junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, xeroderma pigmentosum, lamellar ichthyosis and Netherton syndrome, but so far only one patient has been treated in a clinical trial. This article reviews the current status of gene therapies for patients with inherited skin diseases and explores future perspectives. Semin Cutan Med Surg 33:83-90 © 2014 Frontline Medical Communications
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Jun
2014
Vol. 33. No. 2

Merkel cell carcinoma: current status of targeted and future potential for immunotherapies

Bishr Aldabagh, MD | Jayne Joo, MD | Siegrid S Yu, MD
Merkel cell carcinoma is an aggressive neuroendocrine tumor with a high incidence of local recurrence, regional nodal and distant metastasis, and a high mortality rate. It has been linked to a polyomavirus in addition to immune suppression. Traditionally, treatment options have been limited to surgery and radiation therapy. Better understanding of the molecular pathways of infection and carcinogenesis has provided potential molecular targets and potential immunotherapies which are discussed in this review. Semin Cutan Med Surg 33:76-82 © 2014 Frontline Medical Communications
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Jun
2014
Vol. 33. No. 2

Precision medicine and precision therapeutics: Hedgehog signaling pathway, basal cell carcinoma and beyond

Anne Lynn S. Chang, MD | Shalini V Mohan, MD
Precision medicine and precision therapeutics is currently in its infancy with tremendous potential to improve patient care by better identifying individuals at risk for skin cancer and predict tumor responses to treatment. This review focuses on the Hedgehog signaling pathway, its critical role in the pathogenesis of basal cell carcinoma, and the emergence of targeted treatments for advanced basal cell carcinoma. Opportunities to utilize precision medicine are outlined, such as molecular profiling to predict basal cell carcinoma response to targeted therapy and to inform therapeutic decisions. Semin Cutan Med Surg 33:68-71 © 2014 Frontline Medical Communications
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Jun
2014
Vol. 33. No. 2

Prospects for personalized targeted therapies for cutaneous squamous cell carcinoma

Bishr Aldabagh, MD | John C. Mavropoulos, MD, MPH, PhD | Sarah T Arron, MD, PhD
Targeted therapies for cutaneous squamous cell carcinoma (cSCC) remain limited. Extensive genetic heterogeneity complicates a robust molecular characterization of the evolution of cSCC. Nonetheless, potential targeted therapies for this cancer are under investigation, including the inhibition of epidermal growth factor receptor (EGFR), which may yield promising results. In addition, the emergence of immune checkpoint blockade therapy and vaccine-based methods may provide novel treatment strategies for cSCC that are tailored to the individual patient. Ultimately, a combination of such methods may yield a multi-pronged targeted approach to personalize the treatment of cSCC. Semin Cutan Med Surg 33:72-75 © 2014 Frontline Medical Communications
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