- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Journal: Impact of BRAF and MEK Inhibitors on Gingival Hyperplasia in Melanoma Patients-A Case Report. (Pubmed Central) - Jan 12, 2025
However, due to his overall poor oral hygiene, gingiva remained inflamed and edematous, but was no longer hyperplastic and hyperkeratotic in appearance. This case underscores the importance of recognizing and adequately addressing this complication, as its adverse effect on a patient's quality of life can potentially compromise treatment protocol adherence.
- |||||||||| acetylcysteine solution / Generic mfg., Zelboraf (vemurafenib) / Roche
Journal: Diclofenac Enhances the Response of BRAF Inhibitor to Melanoma Through ROS/p38/p53 Signaling. (Pubmed Central) - Jan 12, 2025
These findings suggested that diclofenac sensitized BRAFi-resistant melanoma cells to BRAFi by increasing ROS release and activating p38/p53 signaling pathway. Diclofenac might serve as a promising adjunct therapy to overcome BRAFi resistance in melanoma treatment.
- |||||||||| Trial completion, Enrollment change, Trial completion date, Trial primary completion date, Tumor mutational burden: CRAFT: The NCT-PMO-1602 Phase II Trial (clinicaltrials.gov) - Jan 8, 2025
P2, N=72, Completed,
An activating PIK3CA mutation (p.E542K) was found at varying allele fractions (range: 4%-15%). Active, not recruiting --> Completed | N=175 --> 72 | Trial completion date: Jun 2025 --> Dec 2024 | Trial primary completion date: Jun 2025 --> Dec 2024
- |||||||||| Zelboraf (vemurafenib) / Roche
Preclinical, Journal: Characterization of Human Melanoma Skin Cancer Models: A step towards Model-Based Melanoma Research. (Pubmed Central) - Dec 19, 2024
The responsiveness of the FT melanoma models to vemurafenib treatment was successfully monitored, demonstrating their validity as a reliable, reproducible, and humane tool for pharmacological testing and drug development...These models not only replicate the complex cellular interactions and gene expression patterns of human tissue but also maintain robustness after melanoma integration. Our findings highlight the potential of these models in revealing cancer mechanisms and therapeutic targets, offering a significant impact on melanoma research and preclinical testing.
- |||||||||| Journal, IO biomarker, Immune cell: CTHRC1 is associated with BRAF(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma. (Pubmed Central) - Dec 12, 2024
Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Review, Journal: A Comprehensive Review of Targeting RAF Kinase in Cancer Targeting RAF Kinase in Cancer. (Pubmed Central) - Dec 11, 2024
This review discusses the clinical advancements in RAF-targeted therapies, with a focus on ongoing efforts to overcome therapeutic resistance and enhance outcomes for cancer patients. It also underscores the persistent challenges in effectively targeting RAF kinase in oncology.
- |||||||||| Enrollment closed, Tumor mutational burden: CRAFT: the NCT-PMO-1602 Phase II Trial (clinicaltrials.gov) - Dec 11, 2024
P2, N=175, Active, not recruiting,
It also underscores the persistent challenges in effectively targeting RAF kinase in oncology. Recruiting --> Active, not recruiting
- |||||||||| Rituxan (rituximab) / Roche, Zelboraf (vemurafenib) / Roche
Diagnostic Challenges and Treatment of Hairy Cell Leukemia in a Patient with Sarcoidosis: A Case Report () - Dec 7, 2024 - Abstract #ASH2024ASH_8391;
Targeted therapy with BRAF inhibitors like vemurafenib has shown significant efficacy, especially in cases where traditional treatments fail or in relapsed/refractory HCL. Conclusion : This case illustrates the treatment outcome of HCL and underscores the importance of thorough evaluation in patients with complex medical histories to differentiate between sarcoidosis sequelae and emerging hematologic malignancies.
- |||||||||| Real World Outcomes in Adult Histiocytosis: 23-Year Canadian Single Center Analysis () - Dec 7, 2024 - Abstract #ASH2024ASH_7458;
Eight patients (72%) required subsequent therapies with cladribine in 4, vemurafenib in 2 and dabrafenib and trametinib combination in 2 patients...High incidence of second hematological malignancies in our small cohort warrants more efforts to establish the association between the two entities. Prospective, multicenter studies with molecular discoveries are needed in adult counterpart of this orphan disease.
- |||||||||| Review, Journal: A critical analysis of design, binding pattern and SAR of benzo-fused heteronuclear compounds as VEGFR-2 inhibitors. (Pubmed Central) - Nov 16, 2024
The present review compiles the information available on benzo-fused heteronuclear compounds including benzimidazole, benzoxazole and benzothiazole in recent years, with emphasis on their design, activity, structure-activity relationship (SAR) and docking analysis for understanding binding interactions in the active site of VEGFR-2. In addition to this, a topological similarity analysis of these compounds is performed taking sorafenib as template, and a comprehensive SAR is proposed for researchers to further explore the anticancer potential of these pharmacophore.
- |||||||||| azacitidine / Generic mfg., Zelboraf (vemurafenib) / Roche
Journal, Epigenetic controller: Epigenome reprogramming through H3K27 and H3K4 trimethylation as a resistance mechanism to DNA methylation inhibition in BRAFV600E-mutated colorectal cancer. (Pubmed Central) - Nov 16, 2024
In addition to this, a topological similarity analysis of these compounds is performed taking sorafenib as template, and a comprehensive SAR is proposed for researchers to further explore the anticancer potential of these pharmacophore. In conclusion, DNA hypomethylation by 5-azacitidine exhibits a close association with H3K27me3 and PRC activity in BRAFV600E CRC, and simultaneous blockade of DNMT and EZH2 holds promise as a potential therapeutic strategy for patients with BRAFV600E-mutated CRC.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Journal: ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology. (Pubmed Central) - Nov 13, 2024
Validating these results, we demonstrated ERK hyperactivation in patient biopsies from vemurafenib-induced Grover disease, but also from spontaneous Grover disease, revealing a common etiology for both. Finally, in line with our recent identification of ERK hyperactivation in Darier disease, a genetic disorder with identical pathology to Grover disease, our studies uncovered that the pathogenic mechanisms of these two diseases converge on ERK signaling and support MEK inhibition as a therapeutic strategy.?.
- |||||||||| PK/PD data, Preclinical, Journal: Development and validation of an LC-MS/MS method for simultaneous quantification of eight drugs in plasma and brain: Application in a pharmacokinetic study in mice. (Pubmed Central) - Nov 13, 2024
A selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantitation of a cassette of 8 drugs, including docetaxel, erlotinib, loperamide, riluzole, vemurafenib, verapamil, elacridar and tariquidar. Similarly, the precision for all compounds at three different concentration levels ranged below 15
- |||||||||| Opdivo (nivolumab) / BMS, Braftovi (encorafenib) / Pfizer, Mektovi (binimetinib) / Pfizer
Enrollment closed: Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma (clinicaltrials.gov) - Nov 12, 2024
P1, N=14, Active, not recruiting,
Similarly, the precision for all compounds at three different concentration levels ranged below 15 Recruiting --> Active, not recruiting
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tagrisso (osimertinib) / AstraZeneca, Tafinlar (dabrafenib) / Novartis
Journal, Metastases: Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquired BRAF V600E mutation after progression on EGFR-tyrosine kinase inhibitors in advanced EGFR-mutated non-small cell lung cancer patients. (Pubmed Central) - Nov 7, 2024
NGS analysis identified major resistance mechanisms following the triple-targeted therapy, including the EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and an off-target mechanism. EGFR/BRAF/MEK triple-targeted therapy is an effective and safe approach for treating EGFR-mutated NSCLC patients resistant to EGFR-TKIs with acquired BRAF V600E mutations.
- |||||||||| Efficacy of Small Molecule Kinase Inhibitors in Histiocytic Neoplasms with Non-BRAFV600E Mutations: Concordance of Pre-Clinical Predictions to Clinical Responses (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6000;
In contrast, RAF-regulated MAP2K1 mutants have variable sensitivities to allosteric MEK inhibitors (binimetinib, cobimetinib, selumetinib, trametinib) while RAF-dependent and RAF-independent MAP2K1 mutations are resistant...Among those with BRAF class II mutations, 2 received vemurafenib and had NR, while 9 received MEK inhibitors (binimetinib, cobimetinib, trametinib) and most responded (3 CRs, 5 PRs)...There was concordance of efficacy in the setting of BRAF classes I-III and MAP2K1 RAF-regulated mutations. However, we found discordant findings in patients harboring RAF-dependent and RAF-independent MAP2K1 mutations as well as KRAS mutations as most responded to allosteric MEK inhibitors.
- |||||||||| Efficacy of Targeted Agents and Immune Checkpoint Inhibitors in Patients with Malignant Histiocytosis (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5999;
TAs included BRAF inhibitor (vemurafenib [1]), MEK inhibitors (binimetinib [1], cobimetinib [2], trametinib [2]) and others (dasatinib [1], pazopanib [1], pexidartinib [1]), while ICIs were exclusively pembrolizumab (5)...TAs included BRAF inhibitor only (vemurafenib [3], dabrafenib [3]), MEK inhibitor only (trametinib [5]), BRAF + MEK inhibitors (2), and others (apatinib, anlotimib, bevacizumab, daratumumab, dasatinib, imatinib, pazopanib, sorafenib, or combinations [9]), while ICIs included pembrolizumab (4), nivolumab (4), tislelizumab (1), and sintilimab (1)...Conclusion TAs and ICIs can be considered in the management of MH. The responses to ICI therapy may be associated with the degree of PDL1 expression
- |||||||||| Clinical, Retrospective data, Review, Journal, IO biomarker, Metastases: New emerging treatment options for metastatic melanoma: a systematic review and meta-analysis of skin cancer therapies. (Pubmed Central) - Nov 1, 2024
The study underscores the evolving treatment landscape in melanoma management, with a potential shift towards immune checkpoint inhibitors in the adjuvant setting, particularly for BRAF-mutated disease. However, limitations in meta-analysis methodologies and the need for long-term investigations into treatment implications on survival and quality of life underscore the importance of continued research.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, PARP Biomarker, IO biomarker: A new cannabigerol derivative, LE-127/2, induces autophagy mediated cell death in human cutaneous melanoma cells. (Pubmed Central) - Oct 31, 2024
Cell proliferation of the cells after the treatment with LE-127/2, parent CBG or vemurafenib was assessed by Cell Titer Blue Assay...LE-127/2 also induced the expression of some proteins involved in apoptosis, and it is particularly noteworthy the increased level of cleaved PARP. Based on the results obtained, it can be concluded that LE-127/2 induced autophagy could lead to the inhibition of cell proliferation and death in melanoma cells.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
Journal, PD(L)-1 Biomarker, IO biomarker: Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study. (Pubmed Central) - Oct 29, 2024
P=N/A
Triple combination of atezolizumab, vemurafenib, and cobimetinib had proven its efficacy and tolerability in real settings. No impact of potential predictive biomarkers was seen (NCT05402059).
- |||||||||| Zelboraf (vemurafenib) / Roche
Biomarker, Trial completion date, Metastases: Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial) (clinicaltrials.gov) - Oct 22, 2024
P2, N=4, Active, not recruiting,
Active, not recruiting --> Completed Trial completion date: Sep 2024 --> Sep 2025
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Spliceosomal modulation induces immunogenicity of melanoma cells and in vivo immune response (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1375;
Conclusions In summary, these results suggest a therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2 and support the potential of 2155-14 and 2155-18 as drug candidates for the treatment of melanoma. Additionally, it demonstrates the potential of spliceosomal inhibition to stimulate immune system response, suggesting the possibility of using such therapies in combination with FDA-approved immunotherapies.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
Trial completion: IMspire150: A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma (clinicaltrials.gov) - Oct 1, 2024
P3, N=514, Completed,
Additionally, it demonstrates the potential of spliceosomal inhibition to stimulate immune system response, suggesting the possibility of using such therapies in combination with FDA-approved immunotherapies. Active, not recruiting --> Completed
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: CD68-Negative Histiocytoses with Cardiac Involvement, Associated with COVID-19. (Pubmed Central) - Sep 29, 2024
We demonstrated a case of Erdheim-Chester disease in a 67-year-old man with pericardial involvement and positive dynamics with vemurafenib treatment, an autopsy case of xanthogranulomatous myopericarditis in a 63-year-old man, surgical material of xanthogranulomatous constrictive pericarditis in a 57-year-old man, and an autopsy case of xanthogranulomatosis in a 1-month-old girl...This potential indirect association between COVID-19 and the development of histiocytosis in these patients warrants further investigation. To substantiate this hypothesis, more extensive research is needed.
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