Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye. In women, melanomas most commonly occur on the legs; while in men, on the back. Melanoma is frequently referred to as malignant melanoma. However, the medical community stresses that there is no such thing as a 'benign melanoma' and recommends that the term 'malignant melanoma' should be avoided as redundant.
Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ERBB2 gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently referred to as HER2 or CD340.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.
Indole-3-carbinol (I3C, C9H9NO) is produced by the breakdown of the glucosinolate glucobrassicin, which can be found at relatively high levels in cruciferous vegetables such as broccoli, cabbage, cauliflower, brussels sprouts, collard greens and kale. It is also available in dietary supplements. Indole-3-carbinol is the subject of on-going biomedical research into its possible anticarcinogenic, antioxidant, and anti-atherogenic effects. Research on indole-3-carbinol has been conducted primarily using laboratory animals and cultured cells. Limited and inconclusive human studies have been reported. A recent review of the biomedical research literature found that "evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent" and "larger randomized controlled trials are needed" to determine if supplemental indole-3-carbinol has health benefits.
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene.
John Kuriyan is the dean of basic sciences and a professor of biochemistry at Vanderbilt University School of Medicine. He was formerly the Chancellor's Professor at the University of California, Berkeley in the departments of molecular and cell biology (MCB) and chemistry, a faculty scientist in Berkeley Lab's physical biosciences division, and a Howard Hughes Medical Institute investigator. He is a member of the National Academy of Sciences and he has also been on the Life Sciences jury for the Infosys Prize in 2009, 2019 and 2020.
Alexander Levitzki is an Israeli biochemist who is a professor of biochemistry at the Alexander Silberman Institute of Life Sciences, the Hebrew University of Jerusalem.
BRAF is a human gene that encodes a protein called B-Raf. The gene is also referred to as proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B, while the protein is more formally known as serine/threonine-protein kinase B-Raf.
Christopher John Marshall FRS FMedSci was a British scientist who worked as director of the Division for Cancer Biology at the Institute of Cancer Research. Marshall was distinguished for research in the field of tumour cell signalling. His track record includes the discovery of the N-Ras oncogene , the identification of farnesylation of Ras proteins, and the discovery that Ras signals through the MAPK/ERK pathway. These findings have led to therapeutic development of inhibitors of Ras farnesylation, MEK and B-Raf.
Joseph Schlessinger is a Yugoslav-born Israeli-American biochemist and biophysician. He is chair of the Pharmacology Department at Yale University School of Medicine in New Haven, Connecticut, as well as the founding director of the school's new Cancer Biology Institute. His area of research is signaling through tyrosine phosphorylation, which is important in many areas of cellular regulation, especially growth control and cancer. Schlessinger's work has led to an understanding of the mechanism of transmembrane signaling by receptor tyrosine kinases and how the resulting signals control cell growth and differentiation.
Vemurafenib (INN), sold under the brand name Zelboraf, is a medication used for the treatment of late-stage melanoma. It is an inhibitor of the B-Raf enzyme and was developed by Plexxikon.
A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers.
Encorafenib, sold under the brand name Braftovi, is a medication for the treatment of certain melanoma cancers. It is a small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway. This pathway occurs in many different cancers including melanoma and colorectal cancers. The substance was being developed by Novartis and then by Array BioPharma. In June 2018, it was approved by the FDA in combination with binimetinib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.
Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used in combination with vemurafenib (Zelboraf) alone or with both vemurafenib and atezolizumab (Tecentriq) to treat melanoma. Cobimetinib is a MEK inhibitor. Cotellic, Zelboraf, and Tecentriq are all marketed by Genentech.
Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. Inappropriate activation of the pathway has been shown to occur in many cancers. In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib. It was developed by Array Biopharma.
Kevan Michael Shokat is an American chemical biologist. He is a Professor and chair in the Department of Cellular and Molecular Pharmacology at University of California, San Francisco, a professor in the Department of Chemistry at University of California, Berkeley, and an Investigator with the Howard Hughes Medical Institute.
BRAF-activated non-protein coding RNA is a noncoding RNA that in humans is encoded by the BANCR gene. Long non-coding RNAs (lncRNAs) are involved in the intricate network of cancer and contribute significantly to tumorigenesis and progression. BRAF activated non-coding RNA (BANCR), a 693-bp four-exon transcript, was first identified in 2012 as an oncogenic long non-coding RNA in BRAFV600E melanomas cells and was found to be associated with melanoma cell migration. Apart from melanoma, growing evidence has implicated BANCR in the development and progression of a variety of other human malignancies, including retinoblastoma, lung cancer, and gastric cancer, since its discovery. The pattern of expression of BANCR varies according to the kind of cancer, acting as either a tumour suppressor or an accelerator. Functional BANCR may be a useful biomarker for cancer diagnosis and prognosis assessment. BANCR-targeted therapy may also prove to be a promising new treatment option for human cancers.
Richard Malcolm Marais is Director of the Cancer Research UK (CRUK) Manchester Institute and Professor of Molecular Oncology at the University of Manchester.
Antoni Ribas is a Spanish American physician–scientist. He is a Professor of Medicine, Surgery, and Molecular and Medical Pharmacology at the University of California, Los Angeles (UCLA) and Director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center. Ribas served as president of the American Association for Cancer Research (AACR) in 2021–2022.
