566 Results Found

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths globally. BRAF mutation is present in about 10% of CRC patients and is associated with a poor response to chemotherapy. These patients have a relatively poor prognosis. This...

According to clinical trials, BRAF kinase inhibitors in combination with MEK kinase inhibitors are among the most promising chemotherapy regimens for the treatment of advanced BRAF-mutant melanoma, though the rate of BRAF mutation gene-bearing cutane...

The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway th...

Background: There are no active treatment options for patients with progressive melanoma brain metastases (MBM) failing immune checkpoint blockade (ICB) and BRAF/MEK inhibitors (BRAF/MEKi). Regorafenib (REGO), an oral multi-kinase inhibitor (incl. RA...

The Kirsten rat sarcoma viral oncogene homolog (RAS)/v-raf-1 murine leukemia viral oncogene homolog 1 (RAF)/mitogen-activated protein kinase 1 (MAPK) signaling cascade is the most important oncogenic pathway in human cancers. Tumors leading mutations...

BRAFV600E is the most frequent oncogenic mutation identified in papillary thyroid cancer (PTC). In PTC patients who do not respond to standard treatment, BRAF inhibitors are currently tested as alternative strategies. However, as observed for other t...

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic...

Understanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, whi...

Background: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug–drug interactions (DDI) on the toxicity profile of anti-BRAF/anti...

Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF i...

Immune checkpoint inhibitors (ICIs), namely programmed cell death 1 (PD-1) or cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors, are currently the standard of care for the treatment of advanced melanoma, with robust and durable responses in a subs...

The advent of mitogen-activated protein kinase (MAPK) inhibitors that directly inhibit tumor growth and of immune checkpoint inhibitors (ICI) that boost effector T cell responses have strongly improved the treatment of metastatic melanoma. In about h...

Background/Objectives: The recent discovery of BRAF mutation in papillary craniopharyngiomas opened new avenues for targeted therapies to control tumour growth, decreasing the need for invasive treatments and relative complications. The aim of this s...

Being a component of the Ras/Raf/MEK/ERK signaling pathway crucial for cellular responses, the VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has emerged as a promising target for anticancer drug discovery due to oncogenic mutations th...

BRAF inhibitors have improved the treatment of advanced or metastatic melanoma in patients that harbor a BRAFT1799A mutation. Because of new insights into the role of aberrant glycosylation in drug resistance, we designed and studied three novel vemu...

Background: Melanoma cancer represents the most lethal type of skin cancer originating from the malignant transformation of melanocyte cells. Almost 50% of melanomas show the activation of BRAF mutations. The identification and characterization of BR...

BRAF and MEK inhibitors (BRAFi and MEKi) are the standard of care for the treatment of metastatic melanoma in patients with BRAFV600E mutations, greatly improving progression-free survival. However, the acquisition of resistance to BRAFi and MEKi rem...

Introduction: The combination of BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved survival in melanoma patients with BRAF V600 mutations. However, these agents can cause cardiovascular (CV) toxicity, compromising efficacy. This study ev...

Background: Although BRAF inhibitors, such as vemurafenib, produce a marked response in patients with advanced melanoma with a BRAF V600 mutation, they eventually develop resistance to this treatment. To address this issue, vemurafenib is increasingl...

BRAF and MEK inhibitor (BRAFi/MEKi) combinations are currently the standard treatment for patients with BRAFV600 mutant metastatic melanoma. Since the RAS/RAF/MEK/ERK-pathway is crucial for the function of different immune cells, we postulated an eff...

The advent of immune-checkpoint inhibitors (CPI) and BRAF/MEK-directed targeted therapy (TT) has improved the treatment landscape of patients with BRAFV600-mutant metastatic melanoma. While TT allows for rapid disease control, the development of seco...

The success of the first approved kinase inhibitor imatinib has spurred great interest in the development of type II inhibitors targeting the inactive DFG-out conformation, wherein the Phe of the DFG motif at the start of the activation loop points i...

BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected...

Targeted therapy with BRAF and MEK inhibitors (BRAFi, MEKi) is one of the mainstays of melanoma treatment. When dose-limiting toxicity (DLT) is observed, an option represents the intra-class switch to a different BRAFi+MEKi combination. Currently, th...

Purpose: This meta-analysis summarizes the incidence of treatment-related adverse events (AE) of BRAFi and MEKi. Methods: A systematic search of Medline/PubMed was conducted to identify suitable articles published in English up to 31 December 2021. T...

B-RAF is a serine/threonine kinase that plays a crucial role in the MAPK signaling pathway, regulating cell proliferation and survival. Mutations in B-RAF, particularly V600E, are associated with several malignancies, including melanoma, colorectal c...

This systematic review investigated the literature on acquired v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor resistance in patients with melanoma. We searched MEDLINE for articles on BRAF inhibitor resistance in patients with melano...

No head-to-head studies exist comparing BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) combination treatments for BRAF-mutant melanoma. A side-by-side analysis of randomized phase III trials is presented that evaluated dabrafenib/trametinib, vemurafenib/c...

High-dose ascorbate paradoxically acts as a pro-oxidant causing the formation of hydrogen peroxide in an oxygen dependent manner. Tumor cells (in particular melanoma cells) show an increased vulnerability to ascorbate induced reactive oxygen species...

Because BRAF-mutated melanomas are addicted to the Mitogen Activated Protein Kinase (MAPK) pathway they show a high response rate to BRAF and MEK inhibitors. However, the clinical responses to these inhibitors are often short-lived with the rapid ons...

The use of BRAF and MEK inhibitors for patients with BRAF-mutant melanoma is limited as patients relapse on treatment as quickly as 6 months due to acquired resistance. We generated trametinib and dabrafenib resistant melanoma (TDR) cell lines to the...

Introduction: BRAF inhibitors (BRAFi), commonly used in BRAF-mutated metastatic melanoma (MM) treatment, frequently cause arthralgia. Although this is one of the most common side effects, it has not been characterized yet. Methods: We retrospectively...

Despite significant progress in melanoma survival, therapeutic options are still needed in case of progression under immune checkpoint inhibitors (ICI), and resistance to targeted therapies (TT) in BRAF-mutated melanomas. This study aimed to assess t...

We reviewed the literature to assess the efficacy and risk of constitutional, cardiac, gastrointestinal, and dermatological toxicities of combined BRAF plus MEK inhibitors versus BRAF inhibitors alone in patients with metastatic melanoma with BRAF mu...

Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma ce...

Histone deacetylase inhibitors (HDACI) are epigenetic compounds that have been widely considered very promising antitumor agents. Here, we focus on the effects of the pan-HDAC inhibitor ITF2357 (Givinostat) in comparison with SAHA (Vorinostat) in mel...

Serine–threonine protein kinase B-RAF (BRAF)-mutated metastatic melanoma (MM) is a highly aggressive type of skin cancer. Treatment of MM patients using BRAF/MEK inhibitors (BRAFi/MEKi) eventually leads to drug resistance, limiting any clinical...

Skin cancer treatment is a combination of BRAF and MEK kinase inhibitors administered as tablets, along with immunotherapy treatment (treatment into the vein) with a group of drugs that inhibit the activity of the immune barrier proteins PD-1 and PDL...

In the last two decades, an increasing number of so-called molecular-targeted therapies have become available for the treatment of patients with advanced malignancies. These drugs have included inhibitors of proteins in the MAPK pathway, such as BRAF...

RAF family proteins are serine–threonine kinases that play a central role in the MAPK pathway which is involved in embryogenesis, cell differentiation, cell proliferation and death. Deregulation of this pathway is found in up to 30% of all human canc...

BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable i...

In BRAFV600mut metastatic melanoma, the combination of BRAF and MEK inhibitors (BRAFi, MEKi) has undergone multiple resistance mechanisms, limiting its clinical benefit and resulting in the need for response predicting biomarkers. Based on phase III...

B-Rapidly Accelerated Fibrosarcoma (BRAF) mutations are found in about 50% of melanoma patients. Treatment with Food and Drug Administration (FDA)-approved BRAF and MAP/ERK kinase (MEK) inhibitors has improved progression free and overall survival of...

The introduction of v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors in melanoma patients with BRAF (V600E) mutations has demonstrated significant clinical benefits. However, rarely do tumours regress completely. Frequently, the reason...

BRAFV600E, the most common genetic alteration, has become a major therapeutic target in thyroid cancer. Vemurafenib (PLX4032), a specific inhibitor of BRAFV600E kinase, exhibits antitumor activity in patients with BRAFV600E-mutated thyroid cancer. Ho...

Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and...

B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (...

Activating BRAF mutations occurs in 50–60% of malignant melanomas. Although initially treatable, the development of resistance to BRAF-targeted therapies (BRAFi) is a major challenge and limits their efficacy. We have previously shown that the...

This systematic review and meta-analysis aims to evaluate the efficacy and safety of rechallenging advanced melanoma patients with BRAFi/MEKi. Seven studies, accounting for 400 patients, were included. Most patients received immunotherapy before the...

Despite the success of immune checkpoint inhibitors that target cytotoxic lymphocyte antigen-4 (CTLA-4) and programmed-cell-death-1 (PD-1) in the treatment of metastatic melanoma, there is still great need to develop robust options for patients who a...