pyrimidinones and Intestinal-Neoplasms

To determine the role of BRAF

Topics: Aged; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Neuroendocrine; Cell Line, Tumor; Colorectal Neoplasms; Exons; Female; Follow-Up Studies; G1 Phase Cell Cycle Checkpoints; Humans; Imidazoles; Intestinal Neoplasms; Male; MAP Kinase Signaling System; Mice; Mice, Inbred NOD; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Mutation; Neuroendocrine Tumors; Oximes; Pancreatic Neoplasms; Phosphorylation; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Stomach Neoplasms; Survival Analysis; Tissue Array Analysis; Vemurafenib; Xenograft Model Antitumor Assays

The management of metastatic melanoma has changed significantly in the past decade with the development of immunotherapies and targeted molecular therapies. Trials of targeted therapies have focused mainly on patients with the most common BRAF V600 mutations, namely V600E/K substitutions, with very little information available on the benefit of targeted therapies on less commonly occurring mutations such as V600R/D and M.. We present a 54-year-old man with metastatic melanoma harbouring a rare BRAF V600M mutation, who experienced clinical and radiological response to combined therapy with the BRAF inhibitor dabrafenib and MEK inhibitor trametinib.. As our understanding of these therapies evolves and an increasing number of patients have mutational testing performed, there is a clear imperative--as highlighted by this case--to test for rarer mutations and facilitate their inclusion both in everyday practice and in future clinical trials.

Topics: Abdominal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Humans; Imidazoles; Intestinal Neoplasms; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Molecular Targeted Therapy; Mutation; Oximes; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Neoplasms; Treatment Outcome