Zelboraf (vemurafenib) / Roche 
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  • ||||||||||  Zelboraf (vemurafenib) / Roche
    The small GTPase ARF6 augments BRAF and PI3K expression to promote melanoma survival (Section 26) -  Mar 5, 2024 - Abstract #AACR2024AACR_3992;    
    To test this, we pharmacologically activated ARF6 during serum withdrawal or vemurafenib treatment...In summary, our data suggest that in addition to well-established roles in tumor cell invasion, ARF6 is a crucial mediator of survival during tumor progression and in the context of BRAF targeted therapy. More work is needed to understand how ARF6 activation increases BRAF and PI3K expression and if ARF6 activation contributes to the development of persister cells in melanoma.
  • ||||||||||  RAF709 / Novartis, Zelboraf (vemurafenib) / Roche
    BRAFi-induced ROCK-mediated non-canonical nuclear ?-catenin shuttling drives a phenotypic switch in cancer-associated fibroblasts. (Section 11) -  Mar 5, 2024 - Abstract #AACR2024AACR_3285;    
    In summary, BRAFi reprograms the transcriptional activity in CAFs by driving increased nuclear ?-catenin to increase their ability to remodel the tumor ECM and promote melanoma cell proliferation. Collectively, the data offer new insights into the molecular mechanisms that underlie the paradoxical reprogramming of CAFs by BRAFi in melanoma therapy through the non-canonical ?-catenin pathway.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Accelerating DDR related drug discovery through a customized cell panel (Section 17) -  Mar 5, 2024 - Abstract #AACR2024AACR_2924;    
    Meanwhile, cell cycle, ECM-receptor interaction, and DNA replication are the most enriched KEGG terms. Lastly, we have validated this cell panel against multiple inhibitors targeting different DDR vital proteins such as ATM, PARP, POLQ etc. The result has shown that our unique DDR cell panel is capable of providing fast and comprehensive evaluation of DDR related inhibitors, thus facilitate faster and more efficient discovery of DDR inhibitors in the cancer therapy field.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  Autophagy sustains mitochondrial respiration and determines resistance to BRAFV600E inhibition in thyroid carcinoma cells. (Pubmed Central) -  Mar 4, 2024   
    In agreement, downregulation of the glycolytic pathway results in enhanced mitochondrial respiration and vemurafenib resistance. Our work provides new insights into the role of autophagy in thyroid cancer metabolism and supports mitochondrial targeting in combination with vemurafenib to eliminate BRAFV600E-positive thyroid carcinoma cells.Abbreviations: AMP: adenosine monophosphate; ATC: anaplastic thyroid carcinoma; ATG: autophagy related; ATP: adenosine triphosphate; BRAF: B-Raf proto-oncogene, serine/threonine kinase; Cas9: CRISPR-associated protein; CREB: cAMP responsive element binding protein; CRISPR: clustered regularly interspaced short palindromic repeats; 2DG: 2-deoxyglucose; FA: fatty acid; FAO: fatty acid oxidation; FASN: fatty acid synthase; FCCP: trifluoromethoxy carbonyl cyanide phenylhydrazone; LAMP1: lysosomal associated membrane protein 1; LIPE/HSL: lipase E, hormone sensitive type; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; PRKA/PKA: protein kinase cAMP-activated; PTC: papillary thyroid carcinoma; SREBF1/SREBP1: sterol regulatory element binding transcription factor 1.
  • ||||||||||  Aliqopa (copanlisib) / Bayer, Zelboraf (vemurafenib) / Roche
    Trial completion, Trial completion date:  Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers (clinicaltrials.gov) -  Feb 28, 2024   
    P1,  N=8, Completed, 
    N=1000 --> 3000 Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2023
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  The phenomenon of phototoxicity and long-term risks of commonly prescribed and structurally diverse drugs. (Pubmed Central) -  Feb 23, 2024   
    The following drugs and/or drug classes are discussed: amiodarone, voriconazole, chlorpromazine, doxycycline, fluoroquinolones, hydrochlorothiazide, nonsteroidal anti-inflammatory drugs, and vemurafenib. In reviewing phototoxic skin reactions, this review highlights drug molecular structures, their reactive pathways, and, as there is a growing association between photosensitizing drugs and the increasing incidence of skin cancer, the consequential long-term implications of photocarcinogenesis.
  • ||||||||||  Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
    Recognizing the Rare Erdheim-Chester Disease: Finding Patterns in Pulmonary CT Findings and Other Organ Systems (San Diego Convention Center, Area D (Hall A-B2, Ground Level)) -  Feb 20, 2024 - Abstract #ATS2024ATS_6212;    
    BRAF testing supports the diagnosis but is not always positive and sometimes clinical diagnosis and collaboration with oncology is warranted to effectively treat these patients. It is important to recognize the characteristic findings and pursue available BRAF genetic testing which may be positive and consider directed biologic treatments, Vemurafenib and Cobimetinib.
  • ||||||||||  Gazyva (obinutuzumab) / Roche, Biogen, Zelboraf (vemurafenib) / Roche
    Trial completion date, Trial primary completion date:  A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia (clinicaltrials.gov) -  Feb 15, 2024   
    P2,  N=30, Active, not recruiting, 
    It is important to recognize the characteristic findings and pursue available BRAF genetic testing which may be positive and consider directed biologic treatments, Vemurafenib and Cobimetinib. Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  New Targeted Therapy Combination Holds Promise to Untangle Hairy Cell Leukemia. (Pubmed Central) -  Feb 10, 2024   
    Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing. Hairy cell leukemia (HCL) is an uncommon B-cell neoplasm uniquely characterized by a high prevalence of the BRAFV600E mutation, which leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway.1 In fact, the BRAFV600E point mutation is identified in nearly all cases of HCL; however, it is absent in HCL variant (vHCL) and rare in other B-cell neoplasms.2,3 Notably, in contrast to melanoma or other BRAF mutant solid tumors, HCL exhibits very few other mutations, potentially explaining the high response rates observed in patients treated with mutant BRAF-targeted agents, such as vemurafenib.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  HGF facilitates methylation of MEG3, potentially implicated in vemurafenib resistance in melanoma. (Pubmed Central) -  Jan 30, 2024   
    It was identified that top-hit molecules had better binding and interaction activity than standard in all three classes of mutants. The present study highlights the potential of MEG3 as a pivotal regulator of c-met, establishing it as a promising candidate for targeted drug development in the ongoing pursuit of effective therapeutic interventions.
  • ||||||||||  Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, Tecentriq (atezolizumab) / Roche
    LARGE LEFT VENTRICULAR MASS WITH "LOBSTER CLAW" SIGN (Hall B4-5) -  Jan 26, 2024 - Abstract #ACC2024ACC_5401;    
    He had known melanoma with cerebral, adrenal and hepatic metastases, which is currently treated with atezolizumab, vemurafenib and cobimetinib. We should keep in mind that metastasis is the most common cardiac tumor, especially in patients with known primary malignancy.
  • ||||||||||  Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
    Trial primary completion date:  Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma (clinicaltrials.gov) -  Jan 25, 2024   
    P2,  N=36, Recruiting, 
    We should keep in mind that metastasis is the most common cardiac tumor, especially in patients with known primary malignancy. Trial primary completion date: Oct 2023 --> Oct 2024
  • ||||||||||  Enrollment change, Trial withdrawal:  SMMART Adaptive Clinical Treatment (ACT) Trial (clinicaltrials.gov) -  Jan 23, 2024   
    P1,  N=0, Withdrawn, 
    Trial primary completion date: Oct 2023 --> Oct 2024 N=25 --> 0 | Not yet recruiting --> Withdrawn
  • ||||||||||  Votrient (pazopanib) / Novartis, BeiGene, Rubraca (rucaparib) / Pharma& Schweiz, Zelboraf (vemurafenib) / Roche
    High Grade Endometrial Stromal Sarcoma Patients Treated In A Tertiary Care Oncology Centre In India  (Poster area) -  Jan 18, 2024 - Abstract #ESGO2024ESGO_931;    
    Systemic therapy was given in IIIC= 1, IVA= 1, IVB= 6 (Vemurafenib in 1, 2nd line Rucaparib in 1)...At last follow-up stage IA patients are disease free and alive, 3 out of 7 stage IB expired with relapse in lungs (pazopanib for 5 months), abdominal wall (palliative care for 1 month) and unknown site confirmed on telephonic follow-up...Median follow-up for alive patients was 38 months(IQR 29-48).Conclusion To our knowledge this is the largest series of HGESS reported from India. Stage IB and higher tumors have a poor prognosis and require newer therapeutic strategies to improve outcome.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Trial completion date:  Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas (clinicaltrials.gov) -  Jan 16, 2024   
    P1,  N=40, Active, not recruiting, 
    Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable. Trial completion date: Dec 2023 --> Dec 2025
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal, Oncolytic virus, IO biomarker:  Sox10-Deficient Drug-Resistant Melanoma Cells Are Refractory to Oncolytic RNA Viruses. (Pubmed Central) -  Jan 15, 2024   
    Melanoma resistance to vemurafenib further perturbs the cells' ability to be infected by oncolytic viruses...Interestingly, the induction of ISGs appears to be independent of type I IFN production. Overall, our data suggest that the pathway mediating oncolytic resistance is due to the loss of SOX10 during acquired drug resistance in melanoma.
  • ||||||||||  Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Zelboraf (vemurafenib) / Roche
    Clinical, Review, Journal:  BRAF Inhibitors in BRAF-Mutated Colorectal Cancer: A Systematic Review. (Pubmed Central) -  Jan 11, 2024   
    The hazard ratio of overall survival was also significantly better with triplet encorafenib therapy at 0.52 (95% CI = 0.39-0.70)...PROSPERO registration No. CRD42023471627.
  • ||||||||||  Mekinist (trametinib) / Novartis, BeiGene, Zelboraf (vemurafenib) / Roche, Yervoy (ipilimumab) / Ono Pharma, BMS
    Journal, Metastases:  Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case. (Pubmed Central) -  Jan 9, 2024   
    Monitoring of the temporal dynamics of T cells by analysis of the T cell receptor (TCR) repertoire in the tumor and peripheral blood during disease evolution indicated that T-cell clones with common TCR rearrangements, present at low levels at baseline, were maintained and expanded after immunotherapy, and that TCR diversity increased. Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Trial completion date:  Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma (clinicaltrials.gov) -  Jan 8, 2024   
    P2,  N=17, Active, not recruiting, 
    Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy. Trial completion date: Dec 2023 --> Dec 2024
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  Acquired and intrinsic resistance to vemurafenib in BRAF -driven melanoma brain metastases. (Pubmed Central) -  Jan 4, 2024   
    Although initially responsive, A375 MBMs rapidly developed therapy resistance, even in Abcb1a/b;Abcg2 mice, and this was unrelated to pharmacokinetic or target inhibition issues. Taken together, we demonstrate that both intrinsic and acquired resistance can play a role in MBMs.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Trial completion date:  AcS (clinicaltrials.gov) -  Dec 15, 2023   
    P2,  N=216, Active, not recruiting, 
    Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations. Trial completion date: May 2024 --> Dec 2024
  • ||||||||||  Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Heterogeneity:  DARWIN II: Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity (clinicaltrials.gov) -  Dec 4, 2023   
    P2,  N=50, Active, not recruiting, 
    Trial completion date: May 2024 --> Dec 2024 Recruiting --> Active, not recruiting | N=119 --> 50 | Trial completion date: Nov 2025 --> May 2026 | Trial primary completion date: Nov 2024 --> May 2026