Faculty Bibliography

There have been several significant advances in cancer treatment in the last decade that are applicable to the treatment of melanoma and advanced nonmelanoma skin cancers. Among these are the development of immune checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death legand-1 (PDL-1) axis, as well as targeted inhibitors of the BRAF/MEK signaling cascade in melanoma, and the hedgehog signaling pathway in basal cell carcinoma (BCC). These immune-based and targeted therapies have dramatically changed the treatment options for locally advanced and metastatic melanoma, Merkel's cell carcinoma, cutaneous squamous cell carcinoma (cSCC), and BCC. In this article, we will briefly review the currently approved targeted and immunotherapy-based treatments for locally advanced and metastatic melanoma, Merkel's cell carcinoma, and cSCC and discuss various combinations of approved therapies, as well as emerging therapeutic candidates that are currently in clinical trials, including novel checkpoint inhibitors in development, intratumoral oncolytic agents (viral and nonviral), and various immune-based therapies such as toll-like receptor (TLR) agonists, adoptive T-cell therapy, T-cell costimulation, and innate immune cell therapy. For advanced BCC, we will discuss trials investigating the currently approved smoothened (SMO) inhibitors for neoadjuvant use, emerging SMO inhibitors in development, topical SMO inhibitors, alternative targets in the hedgehog signaling pathway, and the use of anti-PD-1 agents for advanced BCC both alone and in combination with SMO inhibitors.

BACKGROUND:The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. While melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy, or increased exogenous hormones from oral contraceptive pills and hormone replacement, impact MM prevalence and outcome. OBJECTIVE:We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS:A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk, as compared to the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS:Eleven studies met our inclusion criteria. Five studies found no increased risk of MM among IVF users as compared to the general population. Two studies found an increase in MM in clomiphene users. Four studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSIONS:The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates that there may be an increased risk of MM in ever-parous patients treated with IVF. High-quality studies, which include a large number of MM cases and control for well-established MM risk factors, are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

Melanocytic lesions of acral sites are common, with an estimated prevalence of 28-36% in the USA. While the majority of these lesions are benign, differentiation from acral melanoma (AM) is often challenging. AM is a unique subtype of melanoma, with distinct molecular characteristics that are thought to contribute to its high rate of locoregional recurrence and worse prognosis. The advent of dermoscopy has since improved the diagnostic accuracy of AM, resulting in earlier detection and arguably improved survival. Additionally, the identification of unique genomic amplifications in AM invites the potential for future AM-specific targeted therapies. Herein, we discuss the importance of dermoscopy in the diagnosis of acral melanocytic lesions and review the treatment strategies for AM.