Melanoma therapy: Check the checkpoints

Abstract

Recent mutational and translational studies have revealed that the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway plays a key role in melanomagenesis. Mutations in NRAS and BRAF are found in the majority of melanomas resulting in the formation of constitutively active NRAS and BRAF molecules, which leads to the proliferation and survival of melanoma cells through the activation of MEK/ERK signals. Inhibitors of BRAF or MEK significantly extend the progression-free survival and overall survival of melanoma patients compared with conventional chemotherapies. Combining BRAF and MEK inhibitors further enhances the clinical effectiveness. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is an immune checkpoint molecule that downregulates T-cell activation by binding to B7 (CD80/CD86) molecules on antigen-presenting cells. Programmed death receptor ligand 1 on melanoma cells negatively regulates T-cell function by binding to the programmed death-1 (PD-1) receptor on T cells. Antibodies against CTLA-4 and PD-1 also enhance the survival of melanoma patients. In this review, we summarize the clinical effectiveness and adverse events of the BRAF inhibitors, MEK inhibitors and anti-immune checkpoint antibodies in melanoma treatment.

Clinicopathological and prognostic significance of programmed death ligand 1 expression in Korean melanoma patients

“…In fact, PD-L1 shows great significance as a predictor for response to an anti-PD-L1/PD-1 therapeutic agent rather than as a prognostic factor in other malignancies. Nevertheless, there are many reports suggesting PD-L1 as a prognostic factor in various cancers 25-30, although the prognostic impact of PD-L1 expression in melanoma is controversial. Previous studies reported that PD-L1 expression in TCs is not correlated with the survival of patients with melanoma 23, 31.…”

A Novel Signature of 23 Immunity-Related Gene Pairs Is Prognostic of Cutaneous Melanoma

“…As most diagnoses are made in the terminal stage, surgical results are often poor. At present, chemotherapy is the first line of treatment for CM (4), although many cases respond poorly to such regimens due to a high prevalence of adverse drug reactions and resistance to chemotherapeutic agents.…”

A Novel Signature of 23 Immunity-Related Gene Pairs is Prognostic of Cutaneous Melanoma

“…The primary clinical feature of CM is early stage metastasis and most diagnoses are made in the terminal stage, thus surgical results are often poor. At present, chemotherapy is the rst-line treatment for CM [2], although many cases respond poorly to such regimens due to the high prevalence of adverse drug reactions and resistance to chemotherapeutic agents.…”