Jun
2014
Vol. 33. No. 2
Current status and future directions of molecularly targeted therapies and immunotherapies for melanoma
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
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
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
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Jun
2014
Vol. 33. No. 2
Precision medicine and precision therapeutics: Hedgehog signaling pathway, basal cell carcinoma and beyond
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
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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