Melanoma

Abstract

Cutaneous melanoma causes 55 500 deaths annually. The incidence and mortality rates of the disease differ widely across the globe depending on access to early detection and primary care. Once melanoma has spread, this type of cancer rapidly becomes life-threatening. For more than 40 years, few treatment options were available, and clinical trials during that time were all unsuccessful. Over the past 10 years, increased biological understanding and access to innovative therapeutic substances have transformed advanced melanoma into a new oncological model for treating solid cancers. Treatments that target B-Raf proto-oncogene serine/threonine-kinase (BRAF) (Val600) mutations using selected BRAF inhibitors combined with mitogen-activated protein kinase inhibitors have significantly improved response and overall survival. Furthermore, advanced cutaneous melanoma has developed into a prototype for testing checkpoint-modulating agents, which has increased hope for long-term tumour containment and a potential cure. These expectations have been sustained by clinical success with targeted agents and antibodies that block programmed cell-death protein 1 in locoregional disease, which induces prolongation of relapse-free, distant-metastasis-free, and overall survival times.

c‐Rel is a cell cycle modulator in human melanoma cells

“…Chemotherapy could not improve overall survival, and most patients with metastatic melanoma are resistant to chemotherapeutic treatment. Despite recent therapeutic advances with the approval of new drugs targeting immunological checkpoints or crucial signalling pathway kinases, most patients with metastatic melanomas die from their disease . Thus, the identification of potential new targets is crucial for the development of future therapies …”

“…Up to 50% of melanomas harbour activating BRAF mutations (V600E/K/D), and increased BRAF kinase activity leads to activation of the downstream MAPK signalling pathway . In addition to BRAF , a smaller yet considerable proportion of human melanomas bear mutations within the NRAS , PTEN, NF1, c‐KIT and CDKN2A ‐encoding genes . Other signalling pathways which have been implicated in melanoma pathophysiology include PI3K (phosphatidylinositol‐3‐kinase)/AKT and NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) signalling …”

β‐Adrenoceptors as drug targets in melanoma: novel preclinical evidence for a role of β3‐adrenoceptors

“…Additional targeted therapies have been introduced against the kinase MEK, a member of the MAPK family, which is frequently co‐activated with BRAF in melanoma patients (Ryu et al ., ). More recently, targeting the immune system with the use of checkpoint inhibitors is emerging as an elective option for melanoma treatment (Schadendorf et al ., ). However, after the initial results associated with targeted therapies, tumour resistance or relapse of the melanoma lesion has been observed (Mattia et al ., ) suggesting the need for additional therapies to treat melanoma.…”

Patient Attitude towards Videodermatoscopy for the Detection of Skin Cancer: A Cross-Sectional Study

“…MM arises from melanocytes, the pigmented cells in the skin, and is the deadliest skin cancer entity with a steadily rising global incidence [7, 8]. Since MM tumour stage and prognosis are highly associated, early detection of malignant lesions is crucial for a better prognosis [9-11]. Dermatoscopy has a sensitivity of approximately 83% and a specificity of 69% for the detection of MM [12].…”