Introduction The selective BRAF serine-threonine kinase inhibitor vemurafenib is currently part of the standard treatment arsenal of patients with advanced BRAF-mutated melanomas. The most common adverse effects of vemurafenib are cutaneous events, arthralgia, and fatigue. Neutropenia is observed in fewer than 1% of the patients, and no disseminated intravascular coagulation (DIC), thrombocytop...

Resistance to the BRAF inhibitor vemurafenib poses a significant problem for the treatment of BRAFV600E-positive melanomas. It is therefore critical to prospectively identify all vemurafenib resistance mechanisms prior to their emergence in the clinic. The vemurafenib resistance mechanisms described to date do not result from secondary mutations within BRAFV600E. To search for possible mutation...

BACKGROUND Vemurafenib is a selective BRAF-inhibitor that has been approved for the use in patients with advanced BRAF-mutant melanoma. Major adverse events include skin rash, photosensitivity, pruritus, cutaneous squamous-cell carcinoma or keratoacanthoma. OBSERVATION We present the case of a patient experiencing extensive sterile abscess of the scrotum after nine months of treatment with ve...

Treatment with RAF inhibitors such as vemurafenib causes the development of cutaneous squamous cell carcinomas (cSCC) or keratoacanthomas as a side effect in 18% to 30% of patients. It is known that RAF inhibitors activate the mitogen—activated protein kinase (MAPK) pathway and stimulate growth of RAS-mutated cells, possibly accounting for up to 60% of cSCC or keratoacanthoma lesions with RAS m...

BACKGROUND Therapy with vemurafenib, an inhibitor of mutated BRAF, yields a response rate of approximately 50% in patients with metastatic melanoma harboring a BRAF V600E mutation. As an adverse effect of vemurafenib, proliferative disorders of keratinocytes, including squamous cell carcinoma, have been described. Low concentration of vemurafenib as present in the epidermis were found to activa...

Introduction. BRAF kinase inhibitors such as Vemurafenib have shown improvement in overall survival, progression-free survival, and response rates in patients with metastatic melanoma with BRAF V600K mutation. However, there were no cases of complete remission reported in patients with V600K mutation before. Case Presentation. A 53-year-old man with metastatic melanoma and dialysis dependent en...

Abstract Purpose: To investigate themechanism(s) of resistance to the RAF-inhibitor vemurafenib, we conducted a comprehensive analysis of the genetic alterations occurring in metastatic lesions from a patient with a BRAF-mutant cutaneousmelanomawho, after a first response, underwent subsequent rechallengewith this drug. ExperimentalDesign:Weobtainedblood and tissue samples fromapatient diagnose...

Influenza A viruses (IAV) can cause severe global pandemic outbreaks. The currently licensed antiviral drugs are not very effective and prone to viral resistance. Thus, novel effective and broadly active drugs are urgently needed. We have identified the cellular Raf/MEK/ERK signaling cascade as crucial for IAV replication and suitable target for an antiviral intervention. Since this signaling c...

Mutations in the serine/threonine kinase BRAF are found in more than 60% of melanomas. The most prevalent melanoma mutation is BRAF(V600E), which constitutively activates downstream MAPK signalling. Vemurafenib is a potent RAF kinase inhibitor with remarkable clinical activity in BRAF(V600E)-positive melanoma tumours. However, patients rapidly develop resistance to vemurafenib treatment. One re...

UNLABELLED BRAF mutations occur in 10-15% of colorectal cancers (CRCs) and confer adverse outcome. While RAF inhibitors such as vemurafenib (PLX4032) have proven effective in BRAF mutant melanoma, they are surprisingly ineffective in BRAF mutant CRCs, and the reason for this disparity remains unclear. Compared to BRAF mutant melanoma cells, BRAF mutant CRC cells were less sensitive to vemurafen...