- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAF melanoma cells. (Pubmed Central) - Jan 14, 2021 Here, we present a multiparameter genome-wide siRNA screening dataset of genes that when depleted improve the viability and glycolytic response to vemurafenib in BRAF mutated melanoma cells. These datasets are suitable for analysis of genes involved in cell viability and glycolysis in steady state conditions and following treatment with vemurafenib, as well as computational approaches to identify gene regulatory networks that mediate response to BRAF inhibition in melanoma.
- |||||||||| Review, Journal: Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma. (Pubmed Central) - Jan 13, 2021
Collectively, these findings strongly suggest that BRAFi may be exploited as synergistic sensitizers of paclitaxel in treating chemoresistant ovarian cancer. This indirect adjusted meta-analysis suggests a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma. (Pubmed Central) - Jan 9, 2021 We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets...Mechanistically, miR-152-5p targeted TXNIP which affected metastasis and BRAFi altered the methylation status of MIR152 promoter. Our study highlights the crucial role of miR-152-5p on melanoma metastasis after BRAFi treatment and holds significant implying that discontinuous dosing strategy may improve the benefit of advanced BRAF-mutant melanoma patients.
- |||||||||| paclitaxel / Generic mfg.
Preclinical, Journal: Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines. (Pubmed Central) - Jan 9, 2021 Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.
- |||||||||| Herceptin (trastuzumab) / Roche
P2a data, Journal, Tumor Mutational Burden, PD(L)-1 Biomarker, Pan tumor: Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study. (Pubmed Central) - Jan 9, 2021 P2a Overall, 12 of 19 patients (63%) with advanced SGC, treated with chemotherapy-free regimens matched to specific molecular alterations, experienced an objective response. Data from MyPathway suggest that matched targeted therapy for SGC has promising efficacy, supporting molecular profiling in treatment determination.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Clinical, Review, Journal: A Review of the Molecular Pathways Involved in Resistance to BRAF Inhibitors in Patients with Advanced-Stage Melanoma. (Pubmed Central) - Jan 8, 2021 This review aims to describe the impact of BRAFi resistance on the pathogenesis of melanoma, the current status of molecular pathways involved in BRAFi resistance, including intrinsic resistance, adaptive resistance, and acquired resistance. This review will discuss how an understanding of the mechanisms associated with BRAFi resistance may aid the identification of useful strategies for overcoming the resistance to BRAF-targeted therapy in patients with advanced-stage melanoma.
- |||||||||| Journal, Combination therapy: NRAS status determines sensitivity to SHP2 inhibitor combination therapies targeting the RAS-MAPK pathway in neuroblastoma. (Pubmed Central) - Dec 30, 2020
Combinations of SHP2 inhibitors with other RAS pathway inhibitors such as trametinib, vemurafenib, and ulixertinib were synergistic and reversed resistance to SHP2 inhibition in NB in vitro and in vivo. These results suggest for the first time that combination therapies targeting SHP2 and other components of the RAS-MAPK pathway may be effective against conventional therapy-resistant relapsed NB, including those that have acquired NRAS mutations.
- |||||||||| tunlametinib (HL-085) / Tianjin Binjiang Pharma
Trial completion date, Trial primary completion date, Metastases: A PhaseI Study of HL-085 Plus Vemurafenib in Solid Tumor With BRAF V600 Mutation (clinicaltrials.gov) - Dec 17, 2020 P1, N=45, Recruiting, This trial will also evaluate exploratory biomarkers pre- and post-treatment in tissue and blood and their correlation with clinical outcomes. Trial completion date: Aug 2020 --> Aug 2021 | Trial primary completion date: Aug 2019 --> Aug 2021
- |||||||||| everolimus / Generic mfg., paclitaxel / Generic mfg.
Review, Journal, PD(L)-1 Biomarker, IO Biomarker: Recent advances in the management of anaplastic thyroid cancer. (Pubmed Central) - Dec 10, 2020 Surgery should be as complete as possible, securing the airway and ensuring access for nutritional support; the current standard of care of radiotherapy is the intensity-modulated radiation therapy; chemotherapy includes the use of doxorubicin or taxanes (paclitaxel or docetaxel) generally with platin (cisplatin or carboplatin)...These include multitarget tyrosine kinase inhibitors (Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Axitinib, Pazopanib, Pyrazolo-pyrimidine compounds), single target tyrosine kinase inhibitors (Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, PPARγ ligands (e.g. Efatutazone), Everolimus against mTOR, vascular disruptors (e.g. Fosbretabulin), and immunotherapy (e.g. Spartalizumab and Pembrolizumab, which are anti PD-1/PD-L1 molecules)...Other single target mutation agents with fair results are Everolimus when a mutation involving the PI3K/mTOR pathway is detected, Imatinib in case of PDGF-receptors overexpression, and Spartalizumab in case of PD-L1 positive tumors...Since in this tumor several genetic alterations are usually found, the aim is to inhibit or disrupt several pathways: these combination strategies use therapy targeting angiogenesis, survival, proliferation, and may act against both MAPK and PI3K pathways. Investigating new treatment options is eagerly awaited since, to date, even the molecules with the best radiological results have not been able to provide a durable disease control.
- |||||||||| Zelboraf (vemurafenib) / Roche, XL888 / Exelixis, Merck (MSD)
Trial completion date: Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma (clinicaltrials.gov) - Dec 4, 2020 P1, N=21, Active, not recruiting, Investigating new treatment options is eagerly awaited since, to date, even the molecules with the best radiological results have not been able to provide a durable disease control. Trial completion date: Dec 2020 --> Jul 2021
- |||||||||| Zelboraf (vemurafenib) / Roche
[VIRTUAL] High-Risk Multisystem Langerhans Cell Histiocytosis in an Adult () - Dec 2, 2020 - Abstract #ASDP2020ASDP_163; This case represents a rare occurrence of high-risk, multisystem LCH in an adult recognized by dermatopathological investigation with complete response to Vemurafenib. This case reinforces the role of skin biopsy in the evaluation of systemic diseases with cutaneous manifestations and serves as a reminder that LCH should be included in the differential diagnosis of seborrheic-like rashes.
- |||||||||| Zelboraf (vemurafenib) / Roche
Journal: Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells. (Pubmed Central) - Nov 27, 2020 In this study we demonstrate that ~50-60% of melanoma cell lines with vemurafenib resistance acquired in vitro show activation of RhoA family GTPases...Two transcriptional effectors downstream of Rho, MRTF and YAP1, are activated in the Rho BRAFi-resistant cell lines, and resistant cells are more sensitive to inhibition of these transcriptional mechanisms. Taken together, these results support the concept of targeting Rho-regulated gene transcription pathways as a promising therapeutic approach to restore sensitivity to BRAFi-resistant tumors or as a combination therapy to prevent the onset of drug resistance.
- |||||||||| Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
Clinical, Journal, IO Biomarker: Vemurafenib and cobimetinib - induced toxic epidermal necrolysis in a patient with metastatic melanoma. (Pubmed Central) - Nov 27, 2020 Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first-line metastatic immunotherapy with pembrolisumab.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Clinical, Clinical data, Review, Journal: RAF kinase dimerization: implications for drug discovery and clinical outcomes. (Pubmed Central) - Nov 26, 2020 A structural perspective of the DIF, how dimerization impacts inhibitor activation and the structure-based design of next-generation RAF kinase inhibitors with unique mechanisms of action is presented. We also discuss potential fields of application for DIF inhibitors, ranging from non-V600E oncoproteins and BRAF fusions to tumors driven by aberrant receptor tyrosine kinase or RAS signaling.
- |||||||||| Mekinist (trametinib) / Novartis, trametinib, Zelboraf (vemurafenib) / Roche
[VIRTUAL] HISTIOCYTIC SARCOMA: CASE REPORT () - Nov 26, 2020 - Abstract #HEMO2020HEMO_336; Histiocytic sarcoma is a rare disease, corresponding to less than 1% of hematological neoplasms, with aggressive evolution and poor survival, especially in patients with disseminated disease. The best treatment is still a challenge, however, understanding the molecular changes involved in pathophysiology can be extremely important in the discovery of possible targets and new therapeutic options.
- |||||||||| [VIRTUAL] DRESSED FOR SUCCESS: BRAF INHIBITOR DESENSITIZATION AFTER DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYSTEMS (DRESS) () - Nov 21, 2020 - Abstract #ACAAI2020ACAAI_638;
One month later, encorafenib and binimetinib were trialed and discontinued the next day upon recurrence of facial edema, lymphadenopathy, follicular-based erythema on extremities and trunk and rising ALT (99 U/L)...Patient successfully completed desensitization to vemurafenib 960mg and started cobimetinib in 85 days.Discussion This is a rare case of BRAFi-induced DRESS and demonstrates potential cross-reactivity among different BRAFi. Desensitization for DRESS can be successful but should only be considered if the benefits outweigh the substantial risks.
- |||||||||| Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Journal: 7-dehydrocholesterol suppresses melanoma cell proliferation and invasion via Akt1/NF-κB signaling. (Pubmed Central) - Nov 18, 2020 Overall, the present results demonstrated that 7-DHC suppressed melanoma cell proliferation and invasion via the Akt1/NF-ĸB signaling pathway, and 7-DHC key target genes were negatively associated with the prognosis. These findings highlight the potential application of 7-DHC for the treatment of melanoma in the future.
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