- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Review, Journal: Molecular targeted therapy of BRAF-mutant colorectal cancer. (Pubmed Central) - Jun 28, 2019
To date, the best results in second-line treatment have been obtained with a combination of vemurafenib, cetuximab, and irinotecan. Despite these advances, further improvements are needed.
- |||||||||| Zelboraf (vemurafenib) / Roche
Clinical, Journal: Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor. (Pubmed Central) - Jun 25, 2019
Further analysis demonstrated that the baseline lncRNAs for IGF2AS, anti-Peg11, MEG3, Zeb2NAT are independent prognostic factors in BRAF-mutant advanced melanoma patients treated with vemurafenib. Evaluation of plasma lncRNAs expression level for advanced melanoma diagnosis and prognosis evaluation appears to be a safe and valuable method; however, this method requires further validation in larger cohorts and randomized trials.
- |||||||||| Review, Journal, Adverse events: Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. (Pubmed Central) - Jun 25, 2019
Other adverse events are less frequent and the association to one substance is less strong such as anaemia, facial paresis (encorafenib), neutropenia (dabrafenib), skin rash, QTc prolongation and increased liver function tests (vemurafenib). This narrative review provides recommendations for monitoring, adverse event evaluation and management focusing on the clinically relevant side effects of the three regimens.
- |||||||||| Yervoy (ipilimumab) / Ono Pharma, BMS
Biomarker, Journal, IO biomarker: Perspectives in melanoma: Meeting report from the Melanoma Bridge (30 November-2 December, 2017, Naples, Italy). (Pubmed Central) - Jun 22, 2019
Much research is now focused on the identification of biomarkers that can be utilised to help select patients for treatment. These and other recent advances in the management of melanoma were the focus of discussions at the third Melanoma Bridge meeting (30 November-2 December, 2017, Naples, Italy), which is summarised in this report.
- |||||||||| Zelboraf (vemurafenib) / Roche
Preclinical, Journal: Modulation of Luciferase Production in Melanoma Cells in vitro (Pubmed Central) - Jun 22, 2019
The targeted drug vemurafenib suppressed the luciferase production in Mel IL cells, whereas DMSO, which is often used as a drug solvent in experiments with cells, stimulated the luciferase production. Based on the results, it was hypothesized that modulation of reporter protein production in mammalian cells reflects the adaptation of intracellular metabolism to external conditions and may be a source of incorrect interpretations of experiments using reporter proteins.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: A Rare Cause of Uveitis: Vemurafenib (Pubmed Central) - Jun 22, 2019
The uveitis resolved and her vision returned to normal. No sign of recurrence was detected at 8-month follow-up.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
Journal, IO Biomarker: New treatment options in hairy cell leukemia with focus on BRAF inhibitors. (Pubmed Central) - Jun 22, 2019
Identification of the BRAF-V600E kinase mutation as the genetic cause of HCL has opened the way, in the relapsed/refractory experimental setting, to targeted and non-myelotoxic effective strategies that are based on inhibition of BRAF with vemurafenib, co-inhibition of BRAF and its target MEK with dabrafenib and trametinib, and BRAF inhibition with vemurafenib combined with anti-CD20 immunotherapy. In particular, vemurafenib plus rituximab is emerging as a short, safe, chemotherapy-free regimen able to induce deep complete remissions in most HCL patients refractory to, or relapsed multiple times, after chemo(immuno)therapy.
- |||||||||| Braftovi (encorafenib) / Array Biopharma, Ono Pharma, Pierre Fabre, Zelboraf (vemurafenib) / Roche, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Array Biopharma
Clinical, P3 data, Journal, IO Biomarker: Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. (Pubmed Central) - Jun 19, 2019
P3
The combination of encorafenib plus binimetinib provided clinically meaningful efficacy with good tolerability as shown by improvements in both progression-free survival and overall survival compared with vemurafenib. These data suggest that the combination of encorafenib plus binimetinib is likely to become an important therapeutic option in patients with BRAF-mutant melanoma.
- |||||||||| Zelboraf (vemurafenib) / Roche
Clinical, Journal: BRAF Inhibitor-Associated Granulomatous Dermatitis: A Report of 3 Cases. (Pubmed Central) - Jun 19, 2019
Treatment with potent topical and oral steroids improved the eruptions, but only after the cessation of vemurafenib did all 3 cases of granulomatous dermatitis completely resolve within 2 weeks. It is important to recognize that this association, unlike most other BRAF inhibitor-related skin toxicities, can occur many months after commencement of therapy and that vemurafenib treatment can be continued without clinically significant adverse effects.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Vemurafenib impairs the repair of ultraviolet radiation-induced DNA damage. (Pubmed Central) - Jun 17, 2019
The expression of the interferon-related damage resistance signature is decreased upon vemurafenib treatment in 36% of donors. The enhanced rate of NMSC in patients treated with vemurafenib might be partly related to a vemurafenib-driven impaired capacity for DNA repair.
- |||||||||| Journal: BRAF mutation: A promising target in colorectal neuroendocrine carcinoma. (Pubmed Central) - Jun 7, 2019
High frequencies of BRAF mutation and elevated expression levels of pMEK were detected in biologically aggressive and highly proliferative colorectal NECs. We provide evidence that targeting BRAF oncogene may represent a therapeutic strategy for patients with BRAF mutant colorectal NECs.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Identification of a Novel Quinoxaline-Isoselenourea Targeting the STAT3 Pathway as a Potential Melanoma Therapeutic. (Pubmed Central) - Jun 6, 2019
Docking studies further revealed the favorable binding of compound 1 with the SH2 domain of STAT3, suggesting it acts through STAT3 inhibition. Taken together, our results suggest that compound 1 induces apoptosis by means of the inhibition of the STAT3 pathway, non-specifically targeting both B-RAF-mutant and WT melanoma cells, with much higher cytotoxicity than the current therapeutic drug PLX-4032.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal, Cancer stem cells: Melatonin synergizes BRAF-targeting agent vemurafenib in melanoma treatment by inhibiting iNOS/hTERT signaling and cancer-stem cell traits. (Pubmed Central) - Jun 5, 2019
Taken together, our results suggest that compound 1 induces apoptosis by means of the inhibition of the STAT3 pathway, non-specifically targeting both B-RAF-mutant and WT melanoma cells, with much higher cytotoxicity than the current therapeutic drug PLX-4032. Collectively, our results demonstrate melatonin synergizes the antitumor effect of vemurafenib in human melanoma by inhibiting cell proliferation and cancer-stem cell traits via targeting NF-κB/iNOS/hTERT signaling pathway, and suggest the potential of melatonin in antagonizing the toxicity of vemurafenib and augmenting its sensitivities in melanoma treatment.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen, Zelboraf (vemurafenib) / Roche
Journal: Sorafenib induces synergistic effect on inhibition of vemurafenib resistant melanoma growth. (Pubmed Central) - Jun 3, 2019
Compared to the other drugs sorafenib in combination with vemurafenib significantly inhibited proliferation of A375Res cells. These findings show that Sorafenib, in combination with Vemurafenib, is a more effective method for treatment of melanoma with B-Raf 600E mutation.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma. (Pubmed Central) - May 30, 2019
The outcome of this transcriptional plasticity is selection for a set of transcriptional master regulators, which circumvent upstream targeted kinases and provide alternative routes of mitogenic activation. A fine-woven network of redundant signals maintains similar effector genes allowing for tumor cell survival and malignant progression in therapy-resistant cancer.
- |||||||||| Clinical, Journal, IO Biomarker: Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings. (Pubmed Central) - May 29, 2019
Some serious adverse effects, including cutaneous squamous cell carcinoma, are attenuated with combination therapy, while less severe and reversible effects including pyrexia, left ventricular dysfunction, and ocular events can be more common with combination therapy. Existing data are insufficient to recommend triplet therapy, or a particular treatment sequence, with respect to BRAF and MEK inhibitors and immune therapies, though results from multiple ongoing trials are anticipated.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, Zelboraf (vemurafenib) / Roche
Trial completion date, Trial primary completion date, Combination therapy, Surgery, Metastases: Vemurafenib, Cetuximab, and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or That Cannot Be Removed by Surgery (clinicaltrials.gov) - May 29, 2019
P1, N=33, Active, not recruiting,
Existing data are insufficient to recommend triplet therapy, or a particular treatment sequence, with respect to BRAF and MEK inhibitors and immune therapies, though results from multiple ongoing trials are anticipated. Trial completion date: Feb 2019 --> Mar 2024 | Trial primary completion date: Feb 2019 --> Mar 2024
- |||||||||| Mekinist (trametinib) / Novartis, trametinib, Zelboraf (vemurafenib) / Roche
Journal, IO Biomarker: Dual suppression of inner and outer mitochondrial membrane functions augments apoptotic responses to oncogenic MAPK inhibition. (Pubmed Central) - May 24, 2019
Indeed, combined inhibition of the anti-apoptotic BCL-2 repertoire with BH3-mimetics, OXPHOS, and oncogenic MAPK signaling induces fulminant apoptosis and eliminates clonogenic survival. Altogether, these data suggest that dual suppression of IMM and OMM functions may unleash the normally inadequate pro-apoptotic effects of oncogenic MAPK inhibition to eradicate cancer cells, thus preventing the development of resistant disease, and ultimately, supporting long-term remission.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Antitumor properties of RAF709, a highly selective and potent inhibitor of RAF kinase dimers, in tumors driven by mutant RAS or BRAF. (Pubmed Central) - May 22, 2019
Resistance to the RAF inhibitor vemurafenib arises commonly in melanomas driven by the activated BRAF oncogene...Further, RAF709 elicited regression of primary human tumor derived xenograft models with BRAF, NRAS or KRAS mutations with excellent tolerability. Our results support further development of inhibitors like RAF709, which represents a next generation RAF inhibitor with unique biochemical and cellular properties that enables antitumor activities in RAS mutant tumors.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Targeting MEK in vemurafenib-resistant hairy cell leukemia. (Pubmed Central) - May 22, 2019
These studies uncover the intimate connection between BRAF dimerization and TAK632 mode of inhibition and highlight the importance of understanding the impact of BRAF inhibitors on kinase dimerization. No abstract available
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