- |||||||||| Zelboraf (vemurafenib) / Roche
Enrollment change, Trial primary completion date, Metastases: Study of Vemurafenib, Carboplatin, and Paclitaxel (clinicaltrials.gov) - Jan 9, 2020 P1, N=21, Active, not recruiting, N=96 --> 21 | Trial primary completion date: Jul 2019 --> Jul 2020
- |||||||||| Zelboraf (vemurafenib) / Roche
Trial primary completion date, Metastases: Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer (clinicaltrials.gov) - Jan 8, 2020 P2, N=24, Active, not recruiting, N=96 --> 21 | Trial primary completion date: Jul 2019 --> Jul 2020 Trial primary completion date: Nov 2019 --> Nov 2020
- |||||||||| Avastin (bevacizumab) / Roche, Herceptin (trastuzumab) / Roche
Clinical, Review, Journal: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Emerging and Investigational Therapties for the Treatment of Adults With Metastatic Brain Tumors. (Pubmed Central) - Jan 2, 2020 There is insufficient evidence to make recommendations regarding: the use of epidermal growth factor receptor inhibitors erlotinib and gefitinib in patients with brain metastasis due to nonsmall cell lung cancerthe use of BRAF inhibitors dabrafenib and vemurafenib in the treatment of patients with brain metastases due to metastatic melanomathe use of HER2 agents trastuzumab and lapatinib to treat patients with brain metastases due to metastatic breast cancerthe use of vascular endothelial growth factor agents bevacizumab, sunitinib, and sorafenib in the treatment of patients with solid tumor brain metastases. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_9.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Vemurafenib-induced radiation recall dermatitis (Pubmed Central) - Dec 28, 2019 The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_9. Radiation recall dermatitis is a cutaneous reaction that must be known and which in rare cases such as ours may occur a long time after the end of radiotherapy.
- |||||||||| Journal: Identifying the ErbB/MAPK Signaling Cascade as a Therapeutic Target in Canine Bladder Cancer. (Pubmed Central) - Dec 23, 2019
These findings suggest the potential for combined MAPK and ErbB receptor inhibition as a therapy for canine TCC. SIGNIFICANCE STATEMENT: The results of this study (1) identify a novel combination strategy for canine bladder cancer treatment: targeting the ErbB/MAPK signaling cascade and (2) establish the utility of canine bladder cancer as a naturally-occurring model for human MAPK-driven cancers.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: miR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP. (Pubmed Central) - Dec 21, 2019 Moreover, the tumor-suppressive activity of miR-550a-3-5p and its sensitization effect for vemurafenib resistance were also observed in tumor xenograft models. Collectively, our data suggest that miR-550a-3-5p acts as a tumor suppressor through the targeting of oncogenic YAP and may be a new therapeutic tool for YAP-mediated BRAF inhibitor resistance in BRAF-mutant cancer cells.
- |||||||||| sirolimus / Generic mfg.
Journal: Conjunctival Melanoma Targeted Therapy: MAPK and PI3K/mTOR Pathways Inhibition. (Pubmed Central) - Dec 20, 2019 To analyze the activity of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinases/mechanistic target of rapamycin (PI3K/mTOR) pathways in benign and malignant conjunctival melanocytic proliferations and explore whether specific inhibitors can suppress growth of conjunctival melanoma (CJM) cells...WST-1 assays were performed with a BRAF inhibitor (vemurafenib), two MEK inhibitors (trametinib, selumetinib), a PI3K inhibitor (pictilisib), and a dual PI3K/mTOR inhibitor (dactolisib)...The MAPK pathway activity in CJM is increased, not only as a consequence of the BRAF V600E mutation. Targeted therapy may be useful for patients with CJM, especially those with activating BRAF mutations, whereas NRAS-mutated melanomas are relatively resistant.
- |||||||||| Clinical, Review, Journal, Adverse events: Efficacy and Adverse Events in Metastatic Melanoma Patients Treated with Combination BRAF Plus MEK Inhibitors Versus BRAF Inhibitors: A Systematic Review. (Pubmed Central) - Dec 12, 2019
The randomized clinical trials (RCTs) with comparison to vemurafenib monotherapy were included to determine constitutional, gastrointestinal, cardiac, and dermatological toxicities using PRISMA statistical analysis with relative risk (RR) for equal comparison to avoid inclusion bias...BRAF plus MEK inhibitor combination therapy demonstrated overall better efficacy compared to BRAF inhibitor monotherapy. Combination therapies appear to have favorable dermatologic side effect profiles, similar constitutional and cardiac profiles, and slightly worse gastrointestinal profiles compares to monotherapy regimens.
- |||||||||| Zelboraf (vemurafenib) / Roche
Trial primary completion date: Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma (clinicaltrials.gov) - Dec 11, 2019 P2, N=17, Active, not recruiting, Combination therapies appear to have favorable dermatologic side effect profiles, similar constitutional and cardiac profiles, and slightly worse gastrointestinal profiles compares to monotherapy regimens. Trial primary completion date: Dec 2019 --> Apr 2020
- |||||||||| Journal: Repurposing anticancer drugs for targeting necroptosis. (Pubmed Central) - Dec 6, 2019
This review summarizes recent evidence indicating that some anticancer kinase inhibitors also negatively affect necroptosis signaling. This implies that some cancer therapeutics may be repurposed for other pathologies, e.g. ischemic or inflammatory diseases.
- |||||||||| paclitaxel / Generic mfg., Zelboraf (vemurafenib) / Roche
Clinical, P1 data, Journal: Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients With BRAF-mutated melanoma and other advanced malignancies. (Pubmed Central) - Nov 30, 2019 Collectively, our results provide a rationale for use of this drug in MM treatment. The combination of vemurafenib, carboplatin, and paclitaxel is well tolerated and demonstrates encouraging activity, predominantly in patients with advanced melanoma and BRAF mutations, regardless of prior treatment with BRAF and/or MEK inhibitors.
- |||||||||| U0126 / Promega, Zelboraf (vemurafenib) / Roche
Journal: Long glucocorticoid-induced leucine zipper regulates human thyroid cancer cell proliferation. (Pubmed Central) - Nov 28, 2019 Treatment with MAPK inhibitors led to the phosphorylation of the cAMP/response element-binding protein (CREB), and active CREB bound to the L-GILZ promoter, contributing to its transcription. We suggest that the CREB signaling pathway, frequently deregulated in thyroid tumors, is involved in L-GILZ upregulation and that L-GILZ regulates thyroid cancer cell proliferation, which may have potential in cancer treatment.
- |||||||||| Zelboraf (vemurafenib) / Roche
Clinical, Journal: Statistical challenges posed by uncontrolled master protocols: sensitivity analysis of the Vemurafenib study. (Pubmed Central) - Nov 28, 2019 As patient cohorts become ever more refined into smaller targeted subsets, consumers of reports of uncontrolled trials should be further empowered with improvements in reporting practices that better describe the enrolled prognostic subpopulations and importantly their association with study endpoints. This article demonstrates the issue with a sensitivity analysis of the findings reported in a recent trial which was devised to evaluate the preliminary clinical efficacy of vemurafenib in BRAFV600 mutation-positive nonmelanoma cancers.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Journal: Inhibition of MERTK promotes suppression of tumor growth in BRAF mutant and BRAF wild-type melanoma. (Pubmed Central) - Nov 28, 2019 In a BRAF-mutated patient-derived xenograft, treatment with combined UNC2025 and vemurafenib was well-tolerated and significantly decreased tumor growth compared to vemurafenib alone. These data support the use of UNC2025 for treatment of melanoma, irrespective of BRAF or NRAS mutational status, and suggest a role for MERTK and targeted combination therapy in BRAF and NRAS-mutated melanoma.
- |||||||||| Zelboraf (vemurafenib) / Roche
Clinical, Journal: KSRP modulates melanoma growth and efficacy of vemurafenib. (Pubmed Central) - Nov 27, 2019 Using heterologous mRNA reporters, we show that a U-rich element within the 3' untranslated region of KLLN is responsible for KSRP-dependent mRNA decay. These findings implicate that KSRP is an important regulator of melanoma cell growth in part through controlling KLLN mRNA stability.
- |||||||||| Zelboraf (vemurafenib) / Roche
Clinical, Journal, Real-World Evidence: Real-World Toxicity Experience with BRAF/MEK Inhibitors in Patients with Erdheim-Chester Disease. (Pubmed Central) - Nov 22, 2019 With the increasing use of targeted therapies in lung cancer treatments, it is important for clinicians to be aware of potentially toxic effects of novel treatments. Patients with ECD appear to require substantially reduced doses of BRAF and MEK inhibitors but are responsive to these lower doses.
- |||||||||| Zelboraf (vemurafenib) / Roche, XL888 / Exelixis, Merck (MSD)
Clinical, Journal: Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma. (Pubmed Central) - Nov 21, 2019 XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAF-mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAF-mutant melanoma.
- |||||||||| Zelboraf (vemurafenib) / Roche
Surprising diversity of spontaneous MAPK pathway inhibitor resistance within a single melanoma cell line () - Nov 21, 2019 - Abstract #SMR2019SMR_322; To systematically investigate the diversity of resistance mechanisms in a single cell line, we generated vemurafenibresistant sublines of the widely utilized BRAF-mutant melanoma cell line, A375...The promoters of strongly upregulated genes in the polyclonal populations were enriched for TEAD transcription factor binding sites. Thus, the methods used to derive drug-resistant cells and the size of the founder population can have a major impact on the nature of the resistant cells that are ultimately obtained from the same parental cell population.
- |||||||||| Zelboraf (vemurafenib) / Roche
Sleeping Beauty mutagenesis drives therapeutic resistance in an in vivo model of BRAFV600 mutant Melanoma () - Nov 21, 2019 - Abstract #SMR2019SMR_307; We also identified alterations in the insertional pattern of transposons into the BRAF locus, which we can attribute to additional growth factors present in vivo. Overall this study works to classify previously unidentified mechanisms of resistance to vemurafenib, while also giving key insight into how the microenvironment alters the genetic landscape of therapeutic Resistance.
- |||||||||| Zelboraf (vemurafenib) / Roche
Biomolecular and biological profile of melanoma subtypes selected by reflectance confocal Microscopy () - Nov 21, 2019 - Abstract #SMR2019SMR_290; Taken together, these results show a progressive increase of aggressiveness from DC to CT melanoma-subtypes, while DN seems to have a unique behaviour. This study represents a first step to the creation of an integrated clinical-biomolecular model for melanoma classification for reaching a more accurate patient/ tumor tailored therapeutic approach.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche, XL888 / Exelixis, Merck (MSD)
Trial primary completion date: XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma (clinicaltrials.gov) - Nov 20, 2019 P1, N=36, Active, not recruiting, Our studies provide insight into additional modes of regulation through which fisetin interferes with melanoma growth underscoring its potential therapeutic efficacy in disease progression. Trial primary completion date: Oct 2019 --> Feb 2020
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