Melanoma

Abstract

Melanoma is a common cancer in the Western world with an increasing incidence. Sun exposure is still considered to be the major risk factor for melanoma. The prognosis of patients with malignant (advanced-stage) melanoma differs widely between countries, but public campaigns advocating early detection have led to significant reductions in mortality rates. As well as sun exposure, distinct genetic alterations have been identified as associated with melanoma. For example, families with melanoma who have germline mutations in CDKN2A are well known, whereas the vast majority of sporadic melanomas have mutations in the mitogen-activated protein kinase cascade, which is the pathway with the highest oncogenic and therapeutic relevance for this disease. BRAF and NRAS mutations are typically found in cutaneous melanomas, whereas KIT mutations are predominantly observed in mucosal and acral melanomas. GNAQ and GNA11 mutations prevail in uveal melanomas. Additionally, the PI3K-AKT-PTEN pathway and the immune checkpoint pathways are important. The finding that programmed cell death protein 1 ligand 1 (PDL1) and PDL2 are expressed by melanoma cells, T cells, B cells and natural killer cells led to the recent development of programmed cell death protein 1 (PD1)-specific antibodies (for example, nivolumab and pembrolizumab). Alongside other new drugs - namely, BRAF inhibitors (vemurafenib and dabrafenib) and MEK inhibitors (trametinib and cobimetinib) - these agents are very promising and have been shown to significantly improve prognosis for patients with advanced-stage metastatic disease. Early signs are apparent that these new treatment modalities are also improving long-term clinical benefit and the quality of life of patients. This Primer summarizes the current understanding of melanoma, from mechanistic insights to clinical progress. For an illustrated summary of this Primer, visit: http://go.nature.com/vX2N9s.

Survival and Prognostic Factors in Patients with Malignant Melanoma: Statistical Analysis of 466 Cases Treated between 1998 and 2014

“…This is in accordance with other observations, which set average age at diagnosis at 57 years, almost a decade before most solid tumors [2]. Rather rare in children, it does not spare any age group and is second only to leukaemia for potential life year's loss [3].…”

The Polysaccharide Extracted from <i>Umbilicaria esculenta</i> Inhibits Proliferation of Melanoma Cells through ROS-Activated Mitochondrial Apoptosis Pathway

“…3,4) The emergence of targeted therapy such as BRAF and mitogen-activated protein extracellular kinase (MEK) inhibitors, and immune checkpoint blockade such as anti-CTLA-4 and anti-PD-1 monoclonal antibodies marked great breakthrough in the management of patients with advanced melanoma. 5,6) However, it is also not satisfied that, although these small targeted molecules have been proved to improve patients' QOL to some extent, adverse events such as pyrexia, photosensitivity and secondary cutaneous squamous-cell carcinomas and drug resistance which developed in about half of patients within several months treatment limited their effects. [7][8][9] Due to the characteristics of good efficacy, safety, and less toxicity to normal body tissues and organs, the natural medicine have attracted growing attention.…”

Research projects in the Surgeon-Scientist and Clinician-Investigator programs at the University of Toronto (1987-2016): a cohort study

“…3 Increased understanding of genomics and cellular physiology has created the prospect of "personalized medicine," 4 the notion of tailoring treatment to the specific needs of individual patients. Paradoxically, however, the possibility of personalized or precision medicine coincides with an apparent devaluing of fundamental research in the field of clinical medicine.…”