BRAF V600

The results suggest that [18F] FDG PET-CT radiomic parameters, particularly the SUV max, have the potential to serve as noninvasive tools for predicting the KRAS/BRAF/EGFR mutation status in mCRC patients.

BRAFmutpTERTwt had higher stromal lymphocytes infiltration as compared to BRAFwtpTERTwt tumors, corroborating the transcriptomic findings. To our knowledge this is the first report of a potential link between TERT and the immune microenvironment, offering an explanation for the aggressive nature of BRAFmutpTERTmut PTC.

After removing other diagnostic types that may mimic PA histology, no adult patients with a diagnosis of PA and K-B fusion died after more than 10 years of mean follow-up. These findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome.

The first-line treatment of HCL has recently changed and immunochemotherapy combining cladribine plus rituximab has become the gold standard. In relapsed or refractory forms, other treatments should be discussed in a multidisciplinary consultation meeting and combine BRAF inhibitors with anti-CD20 antibodies, BTK inhibitors or Bcl-2 inhibitors. The choices should be discussed according to the patient's profile but also their biological profile.

In stage III anti-PD-1 therapy or dabrafenib plus trametinib for patients with BRAFV600 mutated melanoma can be discussed. In resected stage IV, nivolumab can be offered, as well as ipilimumab and nivolumab, in selected, high-risk patients...Neoadjuvant therapy with pembrolizumab followed by complete surgical resection and adjuvant pembrolizumab is also recommended...Other second line therapies include therapy with tumor infiltrating lymphocytes and combinations of immune checkpoint inhibitors not used in first line. This guideline is valid until the end of 2026.

OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.

These findings highlight the potential for actionable alterations in most early-stage EOC patients and support the exploration of chemotherapy-free regimens for low- to intermediate-risk groups, as well as targeted maintenance therapy for high-risk individuals.

Molecular detection has shown that the mutation rate of BRAF in gastric LCH is up to 90.9%; more work is needed as the number of cases is small. Current data show a good prognosis for isolated gastric LCH in adults, but long-term follow-up for early detection of disease progression or systemic involvement is necessary.

P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Mar 2025

P1, N=46, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Aug 2023 --> Dec 2024

Primary MMRD is more common than previously reported in gliomas in children, adolescents, and young adults, is enriched in specific molecular subgroups, and is associated with poor outcomes. Accurate detection, genetic testing, early diagnosis through surveillance, and implementation of immunotherapy might improve survival for these patients.

The results indicate the generated tumor ROIs can effectively address the imbalanced data problem. Our proposed method has the potential to facilitate an accurate diagnosis of rare brain tumors using MRI scans.

A stage-based follow-up regimen is proposed, which in the experience of the guideline group covers the optimal requirements, although further studies may be considered. This guideline is valid until the end of 2026.

Unexpectedly, the SNV-selective crRNAs harboring mismatched nucleotides reduce the promiscuous collateral activity of the RfxCas13d ortholog. These findings demonstrate that the CRISPR-Cas13 system can be reprogrammed to target mutant transcripts with single-base precision, showcasing the tremendous potential of this tool in personalized transcriptome editing.

P2, N=243, Completed, GlaxoSmithKline | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Sep 2024

P1/2, N=34, Terminated, Pfizer | Active, not recruiting --> Terminated; Study was terminated due to portfolio re-prioritization and strategic considerations. The decision was not based on any safety concerns and/or regulatory interactions

They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.

During a limited 1.5-year follow-up period, neither a confirmed local recurrence nor a distant organ metastasis occurred in this case. We propose that BRAF fusion variations can occur in metastatic EOCC.

This study provides new insights into overcoming resistance to BRAF and MAPK inhibitors, with implications for treating thyroid cancer and potentially other BRAF-mutant tumors. Future efforts will focus on high-throughput screening approaches to explore ANXA7-targeted therapeutic strategies for thyroid cancer.

However, resistance to BRAF pathway inhibitors is inevitable, leading to disease progression, and a well-defined strategy to overcome these resistance mechanisms is lacking. This review aims to explore the critical challenges in the management of BRAF-mutated NSCLC, providing a comprehensive summary of the current evidence and highlighting ongoing clinical trials that aim to address these critical gaps.

Background/Objective: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. Similarly, the median OS was not reached, with OS rates of 96.4% at 12 months and 92.5% at 24 months. D + T achieved an RFS benefit, with effects sustained beyond the treatment period, indicating positive outcomes in this patient population.

After the advent of systemic therapies, a trial of the combination targeted therapy of dabrafenib plus trametinib toward BRAF V600-mutant nodal cutaneous melanoma showed that all 35 patients achieved a pathological response...For those tumours that do recur in-field, there are now competing therapies like Talimogene laherparepvec or T-VEC. Generally, ART is now used at the first recurrence. The challenge now is to find which melanomas are truly radiosensitive if ART is to have any future role in this scenario.

TBC1D12 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, p = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, p = 0.010), and advanced tumor stages (85.7% vs. 32.5%, p = 0.006) in PTC. This preliminary study for the first time showed a high prevalence of TBC1D12 5'UTR mutations in ATC and indicated an association between TBC1D12 mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.

BRAF mutation analysis can be performed on fixed fine needle aspiration cytology specimens. Although the frequency of the mutation is higher in specimens with higher Bethesda category scores, it could support clinical decision-making in thyroid nodules with intermediate Bethesda category scores.

Both WES and RNAseq results showed gene alterations related to proliferation, cell differentiation, and metabolic processes. These results show that AM share many of the hallmarks of cancer secondary to the presence of oncogenic mutations or activation of oncogenic signaling pathways.

P=N/A, N=13, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Sep 2025

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

Real-world data suggest that adjuvant TT may be associated with better RFS and DMFS in stage III BRAF V600-mutated melanoma compared to ICI.

The lack of association between molecular alteration status and recurrence risk prevailed after multivariable adjustment for tumor stage and perioperative treatment (P=0.82 for KRAS G12C mutation and P=0.43 for any other molecular alteration). NSCLC patients with resected tumors that harbor molecular alterations have the same recurrence risk as patients with tumors without molecular alterations if treated with surgery plus chemotherapy when indicated.

This is a case showing improvement of a craniopharyngioma after treatment with BRAF and MEK inhibitor combinations. The role of BRAF and MEK inhibitor combinations continues to evolve in this space.

P1/2, N=58, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

P2, N=220, Active, not recruiting, Agenus Inc. | Suspended --> Active, not recruiting

We also discuss the clinical relevance of biomarkers, emphasizing their alignment with the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as well as ancillary tests such as BRAF VE1 immunohistochemistry to detect BRAF V600E mutation and molecular techniques such as real-time polymerase chain reaction, matrix-assisted laser desorption ionization-time of flight mass spectrometry and next-generation sequencing. Our proposed standardized minimum criteria for reflex testing prioritize melanomas with Breslow thickness >4 mm or disseminated disease, who will most benefit from enhanced delivery of biomarkers and expedited access to targeted therapies while attempting to balance cost-effectiveness and utilization of public healthcare resources with patient outcomes.

During melanoma development in cdkn2b-/-/tp53-/- frogs, the occurrences of epithelial-to-mesenchymal transition, the reactivation of pigment cell progenitor cell transcriptional states, and the activation in the MAPK, NF-kB, PI3K-Akt, and TGF-β signaling pathways were noted. Overall, cdkn2b-/-/tp53-/- Xenopus tropicalis provides a vertebrate model for investigating the development of CDKN2A germline mutation-induced hereditary melanoma, contributing to the exploration of the pathogenesis of hereditary melanoma in humans.

P2, N=175, Active, not recruiting, German Cancer Research Center | Recruiting --> Active, not recruiting

Approximately 2% of all CRC cases in this study were CLDN18.2 positive and had unfavorable features (e.g., mucinous or poorly differentiated adenocarcinoma, T3-4 disease, lymphatic invasion, BRAF V600E mutation) and deficient MMR status. CLDN18.2 positivity did not have a significant impact on RFS or OS.

Gliomas are tumors arising in the central nervous system, frequently associated with Class I mutations and BRAF fusions. Further research into resistance mechanisms and long-term effects is necessary to optimize treatment strategies. Other therapies, such as everolimus and Selumetinib, also show potential and warrant further investigation.

P=N/A, N=1000, Active, not recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

No abstract available

P3, N=680, Recruiting, Immunocore Ltd | Trial primary completion date: Dec 2026 --> Oct 2027

Bethesda III-VI thyroid nodules with isolated RAS mutations have a low rate of aggressive histopathologic features and are unlikely to recur. Thyroid lobectomy may be sufficient treatment for these tumors.

Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors.