An Overview of the Changing Landscape of Treatment for Advanced Melanoma

Abstract

Melanoma-the deadliest form of skin cancer-leads to thousands of deaths each year. Although melanoma is less common than basal cell and squamous cell skin cancers, melanoma is more dangerous because it is more likely to spread to other parts of the body, such as lymph nodes, if not diagnosed and treated early. Data from the National Cancer Institute indicate a steady rise in new cases of melanoma and, unfortunately, a steady rate in the number of deaths through 2013. Ninety percent of melanomas are linked to inadequate sun protection from ultraviolet rays or the tanning habits of young adults. Over the past 5 years, however, there have been a variety of new pharmacologic treatments for advanced melanoma including immunotherapy, targeted agents (BRAF and MEK inhibitors), and oncolytic viral therapy. In this article, we review the current literature on the treatment of melanoma, with a focus on emerging therapies.

Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab

“…In past reports, the objective response rates were 3.6–16% in advanced melanoma patients given an anti‐PD‐1 antibody followed by ipilimumab . However, ipilimumab therapy is reportedly used more frequently and produces more severe immune‐related adverse events (irAE) than nivolumab . Additionally, ipilimumab is very expensive, as are other immune checkpoint inhibitors (nivolumab and pembrolizumab), increasing state‐sponsored health‐care expenditures.…”

“…4 Nivolumab and pembrolizumab are human monoclonal antibodies directed against the programmed death 1 (PD-1) protein and are among the immunotherapies which inhibit interactions between this receptor and programmed death ligand 1 (PD-L1). 5,6 Combination therapy with nivolumab and ipilimumab is better than anti-CTLA-4 monotherapy in terms of overall survival (OS) and progression-free survival (PFS), although more severe adverse effects have been noted. 7 Nivolumab or pembrolizumab can be used as a first-line treatment for advanced melanoma rather than anti-CTLA-4 monotherapy in Japan, because anti-PD-1 antibody monotherapy has been shown to improve both OS and PFS as compared with CTLA-4 antibody monotherapy.…”

“…[10][11][12] However, ipilimumab therapy is reportedly used more frequently and produces more severe immune-related adverse events (irAE) than nivolumab. 6,13 Additionally, ipilimumab is very expensive, as are other immune checkpoint inhibitors (nivolumab and pembrolizumab), increasing state-sponsored health-care expenditures. Unfortunately, patients have not obtained sufficient benefit from anti-PD-1 antibody followed by ipilimumab, as the response rate has been low despite marked side-effects.…”

A universal anti‐cancer vaccine: Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival

“…3 By blocking inhibitory signals, this therapeutic strategy allows the naturally occurring specific anti-melanoma cytotoxic T cells (CTLs) to execute their immune function and to eradicate the tumor. 4 However, its effective use has multiple challenges. Mechanisms dealing with the resistance to targeted therapy, the tumor heterogeneity, genetic instability and transcriptional plasticity represent a major obstacle to effective treatment, and additional strategies will likely be required to enhance and broaden the anti-tumor activity.…”

Dynamic relationships among tumor, immune response, and microbiota

“…To continue the activation of the T cell, CD28 on the T cell binds to B7.1 molecule, and then cytokine is released from the activated T cell to continue proliferation and activation of T cells as a third signal. CTLA-4 is important for the inactivation of T cells [50][51][52] . To shut down the activation of T cells, CTLA-4 is upregulated to the activated T cell surface.…”