Zelboraf (vemurafenib) / Daiichi Sankyo, Roche, KeChow Pharma - LARVOL DELTA

Reported Patterns and Outcomes of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Associated with Novel Antineoplastic Therapies: A Retrospective Pharmacovigilance Analysis (AAD 2026) - "Introduction: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe, life-threatening drug reaction traditionally linked to anticonvulsants and allopurinol...Positive signals for DRESS were observed with several drugs, including imatinib, vemurafenib, thalidomide, brentuximab vedotin, and temozolomide. In contrast, drugs like nivolumab, rituximab, and denosumab showed negative signals... Our findings describe an emerging association of DRESS syndrome with novel antineoplastic therapies. The varied risk of DRESS across agents within the same class suggests that it is not necessarily a class-wide hypersensitivity. This highlights the need for increased clinician awareness to aid early recognition and prompt drug withdrawal to improve patient outcomes."

Adverse events • Retrospective data • Eosinophilia • Immunology

Isolated Cutaneous Adult Langerhans Cell Histiocytosis treated with Vemurafenib: a case presentation (AAD 2026) - "Although systemic therapy is rarely employed in skin-only LCH, the identification of the BRAF V600E mutation prompted initiation of vemurafenib. CONCLUSION This rapid and durable response highlights the potential utility of vemurafenib as a viable option in patients with refractory skin-limited, BRAF-mutated LCH, though side effects may limit long-term use."

Clinical • Contact Dermatitis • Dermatitis • Immunology • Langerhans Cell Histiocytosis • Musculoskeletal Pain • Psoriasis • BRAF • CD1a • CD68

Treatment with Kinase Inhibitors Plus Myo-Inositol as Re-Differentiating Agents in Iodine-Refractory Thyroid Cancers. (PubMed, Life (Basel)) - "MI may have a synergistic effect at the cellular level, and the possible increase in the re-differentiation of RAIR-TC in patients treated with KIs plus MI may have great clinical relevance. The re-uptake of RAI will be evaluated as the primary endpoint, and Tg values and QoL will be evaluated as the secondary endpoints. The main limitation of this study is that we do not investigate any clinical effects. We will have to postpone the clinical analysis to a later date after the administration of RAI for therapeutic purposes."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Vertical MAPK pathway targeting is required for tumor regression in novel human and mouse models of NF1-inactivated melanoma (AACR 2026) - "While the MEK inhibitor selumetinib has been FDA approved for pediatric patients with Neurofibromatosis type 1 with benign plexiform neurofibromas arising from germline NF1 mutation, MEK inhibitors and other therapies targeting the MAPK pathway have had limited clinical benefit in patients with tumors driven by NF1-inactivation...As anticipated, loss of Nf1 conditioned the response to treatment with a BRAF monomer inhibitor (vemurafenib). While Nf1-inactivated cells were more sensitive to MEK inhibition (trametinib), or combined BRAF/MEK inhibition, as seen by suppression of ERK phosphorylation (pERK), cyclin D1 and DUSP6 expression, and cell proliferation, levels of pERK quickly rebounded. BRAF V600E/NF1/TP53-mutant cells were also transiently sensitive to combined inhibition of BRAF and the positive RAS adaptor SHP2 (using SHP099); with the rebound of pERK mitigated only by MEK, not upstream BRAF/SHP2, inhibition. In mice with established BrafCA/Nf1/Trp53-null tumors..."

Preclinical • Brain Cancer • Glioma • Melanoma • Oncology • Solid Tumor • CCND1 • DUSP6 • NF1

BRAVO: Optimization of the Time and Dosage of Vemurafenib in BRAF Positive Juvenile Patients With Refractory Histiocytosis (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Anna Raciborska | Trial completion date: Mar 2026 ➔ Jun 2027 | Trial primary completion date: Mar 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • BRAF

Targeting human melanoma growth with non-calcemic vitamin d3 hydroxyderivative: A synergistic approach with vemurafenib (AACR 2026) - "The non-calcemic vitamin D₃ derivative 20(OH)D₃, especially when combined with vemurafenib, inhibits human melanoma growth by blocking oncogenic signaling pathways, independent of apoptosis. Due to its natural origin, safety profile, and pathway selectivity, 20(OH)D₃ has strong potential as a preventive and therapeutic agent against melanoma progression and metastasis."

Melanoma • Oncology • Solid Tumor

Anticancer activity of a humanized anti-VEGFR-1 monoclonal antibody and its derived antibody-drug conjugates targeting tumor cells and tumor-microenvironment components (AACR 2026) - "Moreover, in the case of BRAF mutated PDTXs, hD16F7 mAb also enhanced the efficacy of the BRAF inhibitor vemurafenib...The cytotoxic effects of hD16F7-PBD were also demonstrated on GBM organoids by measuring the fluorescence intensity of calcein-AM (viable cells) and propidium iodide (dead cells). In conclusion, the humanized anti-VEGFR-1 mAb hD16F7 and its derived ADCs showed promising antitumor effects on preclinical tumor models that more closely reflect the clinical response.Funding: AIRC IG 2024-ID 30361 and Italian Ministry of Health NRR Plan, grant PNRR-MCNT2-2023-12377670 (CUP F93C24000250007)"

ADC • Biomarker • Tumor cell • Tumor microenvironment • Brain Cancer • Glioblastoma • Melanoma • Oncology • Solid Tumor • FLT1

Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials (AACR 2026) - "Hedgehog pathway inhibitors induced the highest overall rates, ranging from 20-30% with saridegib and glasdegib, and up to 63% with vismodegib. FGFR inhibitors (pemigatinib, infigratinib) and other kinase inhibitors (ripretinib, vemurafenib, sorafenib, AZD0424) demonstrated moderate rates (22-48%). Lower alopecia incidence was reported with aromatase inhibitors (anastrozole, lenostrozole) and the aurora B kinase inhibitor BI 811283, ranging from 9 to 21%...The higher incidences seen with Hedgehog inhibitors, compared with aromatase inhibitors, highlight how pathway-specific disruption of follicular signaling contributes to hair loss. Further research into the molecular mechanisms of these agents may help clinicians better anticipate and manage this side effect."

Clinical • Oncology • BRAF

Combining optimally synthesized quercetin analogs with BRAF inhibitors as a novel synergistic approach to treat melanoma (AACR 2026) - "Consistent with previously published results, the IC50 for Doxorubicin-HCl on SK-Mel28 cells is ~1uM. Next, cells will be chronically grown in a low concentration drug.During stage 2, the synthesized quercetin analogs +/- vemurafenib will be tested on both untreated and vemurafenib-resistant melanoma cells. These experiments will examine the potential synergetic effects of these novel combinations while maximizing the clinical relevance to patients with BRAF-mutated melanoma by potentially mitigating the risk of high doses and prolonged use of vemurafenib."

Melanoma • Oncology • Solid Tumor

Adipocyte-Derived Extracellular Vesicles Endow Melanoma Cells with Stem-like Traits via PGC-1α-Mediated Mitochondrial Reprogramming. (PubMed, Antioxidants (Basel)) - "In particular, these changes were accompanied by the transition towards a stem-like phenotype, characterized by enhanced spherogenic ability and ABCG2 upregulation; interestingly, this led to a reduced in vitro response to the BRAF inhibitor vemurafenib. Mechanistically, an increase in PGC-1α expression was found, resulting in higher mitochondrial mass and activity, ATP synthesis, and ROS overproduction; of note, treatment of melanoma cells with SR-18292 and XCT790, two inactivators of mitochondrial biogenesis, and N-acetylcysteine, a ROS scavenger, successfully counteracted the above EV-related effects, suggesting that mitochondrial function could be targeted to suppress the vesicular interactions between adipose tissue and melanoma. Taken together, these results highlight the crucial role played by EVs in melanoma stroma, pointing out the ability of adipocyte-derived vesicles to sustain cancer aggressiveness via PGC-1α-dependent mitochondrial reprogramming."

Journal • Melanoma • Oncology • Solid Tumor • ABCG2 • CDH2 • VIM

Cotargeting B-Raf and ACLY in Ras mutant cells leads to synergistic loss of cell viability and apoptosis (AACR 2026) - "B-Raf inhibitors Vemurafenib, Dabrafenib and Encorafenib are used clinically in combination with MEK inhibitors Trametinib, Cobimetinib and Binimetinib. All four Ras mutant cell lines showed increased expression of cleaved PARP and the activation of the ER stress pathway regulator ATF4. Finally, the apoptosis stimulated by the combination was shown to be dependent on Caspase-3 activity using Annexin V analysis of HCT116 cells treated with Vemurafenib plus NDI-091143."

Breast Cancer • Colon Cancer • Colorectal Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • ACLY • ANXA5 • ATF4 • BRAF • CASP3 • RAS

BRAF-defined canine urothelial carcinoma organoids as a comparative oncology platform for drug response evaluation (AACR 2026) - "In xenografted mice, six weeks of oral administration of sorafenib or vemurafenib, markedly reduced tumor formation. Mice treated with BRAF inhibitors also showed decreased p-ERK expression in metastatic lesions and lower BRAF mutant allele fractions in circulating tumor DNA, indicating suppression of metastatic progression through inhibition of the BRAF/MAPK pathway. Collectively, our findings demonstrate that canine TCC organoids function as a comparative model bridging human and canine cancers, enabling us to dissect BRAF-dependent oncogenic mechanisms, evaluate anti-metastatic drug efficacy, and monitor treatment response via ctDNA."

Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • Urothelial Cancer • BRAF • MAPK1 • UPK3 • VIM

Mutational signatures in cancer genomes alter short linear protein motifs involved in cellular signaling networks (AACR 2026) - "UV light-induced V600E substitutions in BRAF create a novel polo-like kinase (PLK1)-binding motif, putatively contributing to vemurafenib resistance in melanoma patients...Lastly, motif-rewiring alterations in cellular signaling networks strongly correlated with patient attributes such as smoking status and functional characteristics such as APOBEC gene expression, revealing how lifestyle variables and intrinsic mutagenic programs can potentially reconfigure cellular signaling and protein-protein interactions. Together, our results uncover process-specific proteomic consequences of mutational processes, offering mechanistic insights into cancer etiology and exposing potential therapeutic vulnerabilities."

Lung Cancer • Melanoma • Oncology • Solid Tumor • BRAF • CTNNB1 • DRD • PLK1 • U2AF1

Optimization of the Time and Dosage of Trametinib in BRAF Negative Juvenile Patients (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Anna Raciborska | Trial completion date: Mar 2026 ➔ Jun 2027 | Trial primary completion date: Mar 2026 ➔ Jun 2027 | Trial primary completion date: Mar 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • BRAF

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P4 ➔ P3

Phase classification • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P4 trial • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2028 ➔ Jul 2028 | Trial primary completion date: Dec 2028 ➔ Jul 2028

Trial completion date • Trial primary completion date • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

Inhibitory effect of vemurafenib combined with panobinostat on human anaplastic thyroid cancer cells. (PubMed, Pak J Pharm Sci) - "Ve combined with Pa exerts a synergistic inhibitory effect on the growth and metastasis of FRO and ARO cells, while promoting apoptosis and cellular redifferentiation. This combination may provide a potential therapeutic strategy for ATC."

Journal • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • SLC2A1

Superior efficacy of vemurafenib combined with iodine-131 for lymph node metastatic BRAF-mutant thyroid cancer: a long-term survival analysis. (PubMed, Am J Transl Res) - "The vemurafenib combined with 131I revealed superior efficacy in improving survival and thyroid function recovery in lymph node metastatic BRAF-mutant thyroid cancer."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • CD8

ROLE OF VEMURAFENIB ON NECROPTOTIC CELL DEATH IN SCOPOLAMINE-INDUCED IN-VITRO AND IN-VIVO MODELS OF ALZHEIMER'S DISEASE (ADPD 2026) - "Vemurafenib demonstrated neuroprotective effects by inhibiting necroptosis, reducing oxidative stress, and improving cognitive function in AD models. These findings support its potential as a repurposed therapeutic agent for AD, warranting further investigation into long-term efficacy and clinical translation."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Neuroblastoma • Solid Tumor • IL1B • IL6 • MLKL • RIPK1 • RIPK3 • TNFA

Design, synthesis and antiproliferative, apoptotic, and immunomodulatory properties of new heteroaryl pyridine-linked 1,2,4-oxadiazoles as prospective dual EGFR/BRAFV600E inhibitors. (PubMed, RSC Adv) - "Compounds 20c and 21c exhibited potent inhibition of EGFR, with IC50 values of 71 and 64 nM, respectively, surpassing the reference erlotinib (IC50 = 80 nM). Moreover, compounds 20c and 21c exhibited BRAFV600E inhibitory action with IC50 values of 49 and 41 nM, respectively, which are somewhat less potent than the reference drug Vemurafenib...Compounds 20c and 21c showed a notable decrease in TNF-α and IL-6 levels compared with dexamethasone, suggesting an immunomodulatory effect. Molecular docking further validated the favorable orientation of 20c and 21c within the ATP-binding pocket of EGFR and BRAFV600E. These findings underscore compounds 20c and 21c as innovative dual-target scaffolds with significant promise for anticancer drug development."

IO biomarker • Journal • Oncology • BAX • BCL2 • EGFR • IL6 • TNFA

BEYOND ATHEROSCLEROSIS: A RARE CAUSE OF NSTEMI IN ERDHEIM-CHESTER DISEASE (ACC 2026) - "Case: 64 year old male with ECD on vemurafenib presented with severe chest pain and palpitations... Severe peri-coronary fibrosis represents an uncommon but important manifestation of Erdheim-Chester disease. Recognition of this presentation is critical, as early diagnosis enables timely management and vigilant surveillance for potential cardiovascular complications."

Atherosclerosis • Atrial Fibrillation • Cardiovascular • Cognitive Disorders • Fibrosis • Immunology • Myocardial Infarction • Rare Diseases

BIOPSY-PROVEN DUAL INFILTRATIVE CARDIOMYOPATHY: RARE COEXISTENCE OF AL AMYLOIDOSIS AND ERDHEIM-CHESTER DISEASE (ACC 2026) - "Decision-Making: Treated with bortezomib/lenalidomide/dexamethasone for AL and vemurafenib for ECD with regression of effusion and atrial mass. Concurrent ECD and AL is unique. Cardiac biopsy was pivotal in diagnosis and guiding targeted therapy."

Biopsy • Amyloidosis • Cardiomyopathy • Cardiovascular • Hematological Malignancies • Monoclonal Gammopathy • Pulmonary Disease • Rare Diseases • BRAF