- |||||||||| Review, Journal: Implications of BRAF V600E mutation in gliomas: Molecular considerations, prognostic value and treatment evolution. (Pubmed Central) - Jan 24, 2023
The possibility of introducing targeted therapies into the treatment algorithm represents a paradigm shift for patients with BRAF V600E mutant recurrent high-grade and low-grade glioma and BRAF routine testing should be considered in clinical practice. The focus of this review is to summarize the molecular landscape of BRAF across glioma subtypes and the novel therapeutic strategies for BRAF V600E mutated tumors.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Momordica cochinchinensis (Gấc) Seed Extracts Induce Apoptosis and Necrosis in Melanoma Cells. (Pubmed Central) - Jan 22, 2023
Cytotoxicity correlated with MAPK signalling pathways leading to apoptosis and necrosis induced by triggering tumour necrosis factor receptor-1 (TNFR1), reducing the expression of nuclear factor kappa B (NF-kB), and suppression of BRAF/MEK. This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma.
- |||||||||| Journal, HEOR, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker, Cost-effectiveness, Cost effectiveness, Metastases: Cost-effectiveness of immune checkpoint inhibition and targeted treatment in combination as adjuvant treatment of patient with BRAF-mutant advanced melanoma. (Pubmed Central) - Jan 20, 2023
P3
This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma. For BRAF-mutant advanced melanoma, the vemurafenib-cobimetinib strategy could be considered the most cost-effective treatment at the willingness-to-pay threshold of $150,000.
- |||||||||| Opdualag (nivolumab/relatlimab) / BMS
Journal, Metastases: Opdualag for metastatic melanoma. (Pubmed Central) - Jan 19, 2023
For BRAF-mutant advanced melanoma, the vemurafenib-cobimetinib strategy could be considered the most cost-effective treatment at the willingness-to-pay threshold of $150,000. No abstract available
- |||||||||| Trial completion date, Trial primary completion date, Tumor mutational burden: Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) (clinicaltrials.gov) - Jan 11, 2023
P2, N=720, Recruiting,
Trial completion date: Dec 2022 --> Dec 2023 Trial completion date: Sep 2023 --> Jan 2027 | Trial primary completion date: Jun 2023 --> Jan 2026
- |||||||||| Review, Journal: Novel targeted treatments in hairy cell leukemia and other hairy cell-like disorders. (Pubmed Central) - Jan 10, 2023
The BRAF mutation is missing in SDRPL and SBLPN: mitogen-activated protein kinase 1 (MAP2K1) mutations were found in 40% of SBLPN and VH4-34+ HCL patients, making possible to use MEK inhibitors (MEKi) such as trametinib, cobimetinib or binimetinib in monotherapy or associated with BRAFi...In this article, we will discuss the main mutations identified in HCL and HCL-like disorders and the signaling pathways potentially involved in the pathogenesis of the different hairy cell disorders. We will discuss the results of the recent clinical trials, which will help us to propose an algorithm useful in clinical practice and we will highlight the different new drugs that may be used in the near future.
- |||||||||| Retrospective data, Journal: BRAF and MEK Inhibitors and Their Toxicities: A Meta-Analysis. (Pubmed Central) - Jan 9, 2023
These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations. Our study provides comprehensive data on treatment-related adverse events of BRAFi and MEKi combination therapies, showing related toxicity profiles to offer a helpful tool for clinicians in the choice of therapy.
- |||||||||| Review, Journal: Targeted Therapy for Anaplastic Thyroid Carcinoma: Advances and Management. (Pubmed Central) - Jan 9, 2023
We found that the previously valued therapeutic effect of lenvatinib may be unsatisfactory; combining tyrosine kinase (TK) inhibitors (TKIs) with other agents results in a higher rate of clinical benefit...The AEs reported for all agents are relatively numerous but largely manageable clinically. More clinical trials are expected to further confirm the effectiveness and safety of these targeted drugs for ATC.
- |||||||||| Trial completion date, Trial primary completion date, Tumor mutational burden: CRAFT: the NCT-PMO-1602 Phase II Trial (clinicaltrials.gov) - Jan 4, 2023
P2, N=175, Recruiting,
This study confirmed that the level of hsa_circ_0001005 in exosomes is the key factor affecting drug resistance of melanoma, which provides a new potential therapeutic target for melanoma patients. Trial completion date: Apr 2024 --> Jun 2025 | Trial primary completion date: Apr 2024 --> Jun 2025
- |||||||||| Opdivo (nivolumab) / BMS, Braftovi (encorafenib) / Pfizer, Mektovi (binimetinib) / Pfizer
Trial completion date, Trial primary completion date: Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma (clinicaltrials.gov) - Jan 3, 2023
P1, N=20, Recruiting,
Trial completion date: Dec 2022 --> Dec 2023 Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: 3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells. (Pubmed Central) - Dec 24, 2022
(3) 3BP treatment, which was more effective as monotherapy than combined with PLX, disturbed the metabolic and epithelial-mesenchymal profile of PLX-resistant cells, impairing their proliferation, migration, and invasion and triggering cell death. (4) 3BP monotherapy is a potent metabolic-disrupting agent against PLX-resistant melanomas, supporting the suppression of the malignant phenotype in this type of neoplasia.
- |||||||||| Trial completion date, Trial primary completion date, Tumor mutational burden: My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors (clinicaltrials.gov) - Dec 21, 2022
P2a, N=670, Active, not recruiting,
(4) 3BP monotherapy is a potent metabolic-disrupting agent against PLX-resistant melanomas, supporting the suppression of the malignant phenotype in this type of neoplasia. Trial completion date: Jan 2023 --> Sep 2023 | Trial primary completion date: Jan 2023 --> Sep 2023
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor, Kalydeco (ivacaftor) / Vertex, Zelboraf (vemurafenib) / Roche
Journal: Novel Inhibitors of Breast Cancer Resistance Protein (ABCG2) Among Marketed Drugs. (Pubmed Central) - Dec 19, 2022
Moreover, a mechanistic static model suggested that vemurafenib, bexarotene, dabigatran etexilate, rifapentine, aprepitant, and ivacaftor could almost fully inhibit intestinal BCRP, increasing the exposure of concomitantly administered rosuvastatin over 90%. Therefore, clinical studies are warranted to investigate whether these drugs cause BCRP-mediated DDIs in humans.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Divergent BRAF Inhibitor Resistance Mechanisms Revealed through Epigenetic Mapping. (Pubmed Central) - Dec 19, 2022
In this report, we generated eight matched pairs of vemurafenib sensitive/resistant melanoma lines and subjected these to concurrent RNA-seq and H3K27Ac ChIP-seq analysis...We subsequently verified the 2-class structure in pre-BRAFi and post-relapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAFi resistance.
- |||||||||| Zelboraf (vemurafenib) / Roche
Biomarker, Journal: Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer. (Pubmed Central) - Dec 17, 2022
Relevant drugs targeting core genes were identified based on drug sensitivity analysis, and found that Vemurafenib downregulates the PI3K-AKT pathway and BCL2A1 protein in BC, as confirmed by external data and cellular assays. Briefly, our work establishes and validates an 11-immune escape risk model, and five core prognostic factors that are mined deeply from this model, and elucidates in detail that Vemurafenib suppresses breast cancer by targeting the PI3K/AKT signaling pathway to inhibit the immune escape biomarker BCL2A1, confirms the validity of the prognostic model, and provides corresponding targeted agents to guide individualized treatment of BC patients.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
P1 data, Journal, PD(L)-1 Biomarker, IO biomarker: Phase I trial of pembrolizumab plus vemurafenib and cobimetinib in patients with metastatic melanoma. (Pubmed Central) - Dec 13, 2022
P1
Peripheral blood flow cytometry identified significantly decreased PD1 expression on CD4+ T-cells at 3 and 9 weeks compared to baseline, not corresponding to clinical response. Triple therapy with vemurafenib, cobimetinib and pembrolizumab is associated with high response rates but significant adverse events, leading to early study closure.
- |||||||||| Review, Journal: Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology. (Pubmed Central) - Dec 12, 2022
"Precision oncology" is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from "old" chemotherapies to "new" target-oriented drugs.
- |||||||||| Zelboraf (vemurafenib) / Roche, Visudyne (verteporfin) / Novartis
Journal: Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors. (Pubmed Central) - Dec 9, 2022
YAP governs adaptive resistance to RAF kinase inhibitors and induces a gene expression program in BRAF-mutant cells encompassing effectors in the NRG1 signaling pathway, which play a central role in the insensitivity to MAPK inhibitors in a lineage-dependent manner. HIPPO pathway inactivation serves as a lineage-dependent rheostat controlling the magnitude of the adaptive relief of feedback responses to MAPK inhibitors in BRAF- cancers.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
P3 data, P3 data: top line, Journal, Combination therapy, PD(L)-1 Biomarker: Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAF mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study. (Pubmed Central) - Dec 4, 2022
P3
Additional follow-up of the IMspire150 trial showed that overall survival was not significantly improved with atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobimetinib in patients with BRAF mutation-positive advanced melanoma. Results of the final analysis are awaited to establish whether a significant improvement in overall survival can be achieved with long-term treatment with this triplet combination versus vemurafenib plus cobimetinib.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Trial termination, Metastases: REPOSIT: Vemurafenib Plus Cobimetinib in Metastatic Melanoma (clinicaltrials.gov) - Nov 30, 2022
P2, N=78, Terminated,
We conclude that GCL-driven glutathione synthesis protects BRAF-expressing tumors from oxidative stress during distant metastasis to the liver and the lungs. Unknown status --> Terminated; Slow accrual and changing treatment landscape
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Early molecular diagnosis of BRAF status drives the neurosurgical management in BRAF V600E-mutant pediatric low-grade gliomas: a case report. (Pubmed Central) - Nov 30, 2022
We report two cases of symptomatic PLGG treated with vemurafenib, a BRAF inhibitor: in a 12-year-old girl it was used as first-line medical treatment, reducing the tumor by 45% within a month and stabilizing to 76% after a year; in a 3-year-old boy with no improvement after SIOP LGG 2004 Protocol, vemurafenib induced in only one week a 34% shrinkage and solved the hydrocephalus, avoiding surgical operation. DISCUSSION AND Our cases demonstrate how an early molecular diagnosis of BRAF mutations through the neurosurgical biopsy is essential to promptly start targeted therapies., whose effect can influence both therapeutic and surgical decisions, hopefully reducing the occurrence of second neurosurgery with associated risks of neurological sequelae.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Antisense-oligonucleotide Therapy Targeting BRAF Alleviates Pediatric Brain Tumors with Intractable Epilepsy (Hall B, Level 3) - Nov 29, 2022 - Abstract #AES2022AES_1440;
In our study, ASO therapy targeting BRAF shows strong therapeutic effects on various aspects of BRAF-derived pediatric brain tumors, including the tumor size, epileptic seizures, survival rate, and dysmorphic neurons. Therefore, ASO therapy targeting BRAF will be a promising and effect treatment in BRAF-derived pediatric brain tumors with intractable epilepsy.
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