BRAF V600

Despite poor overall outcomes, incremental progress across targeted, immune, and delivery-based approaches supports a patient centered strategy emphasizing clinical-trial enrollment, molecular profiling and symptom focused care.

The study provides a TT-focused prospective analysis still rare in pediatric oncology. The outcomes indicate satisfactory tolerance and promising efficacy of TT, prompting an update of current treatment standards for several pediatric cancers.

P1/2, N=161, Completed, Takeda | N=109 --> 161

Glioblastoma (GBM) remains associated with poor outcomes, with a median survival of 15-18 months despite maximal safe resection, radiotherapy, and temozolomide. CAR T-cell therapies are advancing toward bispecific and armored constructs with locoregional delivery, while oncolytic viruses such as DNX-2401 and PVSRIPO demonstrate potential for durable responses in select patients. Looking ahead, progress is likely to arise from biomarker-informed, multimodal regimens that integrate targeted agents, next-generation immunotherapies, and precision-guided strategies, while embedding translational endpoints into trial design to address the complex biology and therapeutic resistance of GBM.

P1, N=15, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2026

The analysis revealed an association between the BRAF V600E mutation and papillary thyroid cancer in patients exposed to radiation from nuclear testing at the former SNTS. These findings offer new prospects for targeted therapy and early diagnosis of malignant thyroid neoplasms. Following the closure of the test site, positive developments in public health have been observed: radiophobia has decreased and the population's quality of life has improved. Furthermore, the adoption of iodine prophylaxis legislation and the country's industrial growth have contributed to improved well-being and better epidemiological outcomes for thyroid cancer in subsequent generations.

The Myriapod NGS panel aids in the preoperative assessment of thyroid nodules. Its high negative predictive value may help avoid unnecessary surgery, whereas the detection of specific mutations strongly correlates with malignancy, thus informing surgical planning.

Selective BRAF and MEK inhibitors-including vemurafenib, dabrafenib, and selumetinib-have demonstrated efficacy in advanced thyroid cancers. The combination of dabrafenib and trametinib is FDA-approved for BRAF V600E-mutant anaplastic thyroid carcinoma (ATC) based on its significant survival benefits...Additionally, redifferentiation strategies using MAPK inhibitors to restore RAI avidity have shown promise, particularly in selected patients. These advances highlight the need to contextualize BRAF mutation status within a broader molecular and clinical framework to guide personalized, effective treatment strategies.

At the time of drafting this report, the patient had achieved 8 months of PFS. This case suggests that dose-adjusted dabrafenib combined with trametinib might be a potentially effective treatment strategy for elderly patients with advanced pancreatic adenocarcinoma harboring BRAF V600E mutations.

The generally indolent nature of both tumors supported successful nephron-sparing surgical management. This unique case emphasizes the need for a high index of suspicion for rare tumor subtypes and a multidisciplinary approach to optimize the diagnosis and tailored treatment of complex renal masses.

Compound 7c exhibited the highest potency (GI₅₀ = 6 μM) and was comparably effective to the reference doxorubicin (GI50 = 5 μM) against the four cancer cell lines analyzed...Molecular docking, molecular dynamics (MD) simulations, and DFT analyses revealed key pharmacophoric interactions within the ATP-binding sites of EGFR and BRAFV600E kinases, while in silico ADME predictions supported drug-likeness and showed no PAINS/Brenk structural alerts; however, these predictions do not establish safety, and experimental toxicology will be required. These findings identify compound 7c as a promising dual-target lead candidate for further optimization in anticancer drug development.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.