BRAF mutation

In contrast, FAT1, ATM, BRCA2, LRP1B, and PBRM1 mutations only occurred frequently in patients with DCB, irrespective of PD-L1 expression status. Our study explored molecular signatures of melanoma patients who respond to ICIs treatment and identified a series of mutated genes that might serve as predictive biomarker for ICIs responses in melanoma.

In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

In addition, advancements in genetic testing and an increasing emphasis on precision medicine have led to a more nuanced understanding of these mutations; thus, more granular data for each mutation are reviewed when available. Importantly, such knowledge can pave the way for precision medicine with the ultimate goal of improving patient outcomes.

The investigational regimen did not improve the primary outcome for the intention-to-treat population but might benefit small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer.

Ultimately, this tumor was considered microsatellite stable. Considering the origin of TDA, which is frequently encountered in routine practice, IFN may develop into TDA.

Simulation studies have been conducted to demonstrate the double robustness of the estimators. For illustration, we applied this method to examine the association between pack-years of smoking before the age of 30 and the incidence of colorectal cancer subtypes defined by a combination of four tumor molecular biomarkers (statuses of microsatellite instability, CpG island methylator phenotype, BRAF mutation, and KRAS mutation) in the Nurses' Health Study cohort.

Our study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach.

P1/2, N=1, Terminated, iOx Therapeutics | Trial completion date: Dec 2026 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Apr 2024; Prioritization of other pipeline assets. No safety or efficacy issues were observed.

We presented a case of locally advanced ascending colon cancer in a 17-year-old female patient. CRC rarely occurs in AYAs. However, the incidence has gradually increased in recent years. It should be considered as a differential diagnosis for young patients with long-term abdominal symptoms of unknown cause.

We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. While RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with oncology immune-oncology agents for selected patients with wtRET MTC.

Case Presentation and We report two cases with RAI-resistant lung metastases treated with larotrectinib: 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation)...In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of -0.060. As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

The addition of durvalumab to a gemcitabine plus cisplatin regimen has significantly improved overall survival in the phase 3 TOPAZ-1 trial and is currently recommended as a standard first-line treatment. The phase 3 ABC-06 and phase 2b NIFTY trials have shown the benefit of second-line fluoropyrimidine plus oxaliplatin, and fluoropyrimidine plus nanoliposomal irinotecan, respectively...However, most patients eventually show resistance to the treatment, and tumor progression occurs within a year. Indeed, there should be further efforts to improve the outcomes of patients with advanced IHCCA.

P3; Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P2, N=71, Recruiting, University of Wisconsin, Madison | N=110 --> 71

Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Taken together, these data indicate rapid MAPK reactivation upon MAPKi withdrawal as a tumor cell intrinsic rebound-driving mechanism. Furthermore, increased secretion of microglia-recruiting cytokines may play a role in treatment response and rebound growth upon withdrawal, warranting further evaluation.

P2, N=28, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P1/2, N=162, Recruiting, Tyligand Bioscience (Shanghai) Limited | Not yet recruiting --> Recruiting

P1/2, N=263, Recruiting, Salubris Biotherapeutics Inc | N=149 --> 263

Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.

P1, N=30, Recruiting, Massachusetts General Hospital | N=60 --> 30 | Trial completion date: Sep 2022 --> Sep 2024 | Trial primary completion date: Sep 2022 --> Sep 2024

The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients...We found that cells presenting with minority MOMP-like phenotypes are dependent on the apoptotic regulator, Mcl-1, as treatment with the Mcl-1 inhibitor, AZD5991, potently induced cell death in resistant cells. Furthermore, PI3K/AKT inhibitors sensitized resistant cells to BRAFi; an effect that was at least in part associated with reduced Mcl-1 levels. Together, these data implicate minority MOMP as a mechanism associated with intrinsic drug resistance and underscore the benefits of targeting Mcl-1 in mutant BRAF PTC.

We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors. Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.

P2, N=16, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Jan 2025 --> Apr 2024

P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Jul 2025 | Trial primary completion date: Mar 2025 --> Jul 2025

This study clarified the genetic differences between OMM and NMM, and the first to report the frequent occurrence of RICTOR amplification in OMM. This analysis offers insights into the development of personalized therapeutics for OMM.

In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.

These findings establish a preclinical foundation for the combined use of an anti-HER2 drug conjugate and a BRAF inhibitor in the treatment of BRAF-mutant cutaneous melanoma.

Our data demonstrate that RAS mutations do not affect outcome in rego-treated patients as well as TFD/TPI-treated patients. Nevertheless, a trend toward a higher efficacy of rego in RAS-mutated (in particular codon 12, rare RAS mutations, and G12D) patients has been recorded. The rego-TFD/TPI sequence seems to be superior to the reverse sequence in patients carrying an RAS codon 12 mutation, although the impact of other factors as disease burden or performance status cannot be excluded.

36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.

NRAS mutation in CMs correlated with significantly worse overall survival. Elevated TMB was associated with increased progression-free survival for patients treated with a combination of dual ICI, supporting the potential utility of TMB as a predictive biomarker for ICI response in melanoma.

Erlotinib (EGFR inhibitor) and sulindac (COX inhibitor) were applied individually and in combination. These findings may also facilitate clinical trial design using these agents in SPS patients. Differentially expressed genes identified in our study (MYC, FOSL1, EGR1, IL33, LGR5 and FOXQ1) may be used to identify other new molecular targets for chemoprevention of SSLs.

Our results show promise in supporting the histological classification of these tumours in clinical practice, and provide valuable insight into the use of ML to improve the accuracy and objectivity of this process while minimising interobserver variability. These proposed algorithms represent a potential solution to the lack of a clear threshold for the Spitz/spitzoid tumour classification, and its high accuracy supports its usefulness as a helpful tool to improve diagnostic decision-making.

Importantly, RAD18 depletion in combination with radiotherapy results in marked and sustained tumor regression in KRAS mutant pancreatic cancer orthotopic tumors and BRAF mutant thyroid heterotopic tumors. Overall, our findings identify a novel coordinated RAS/RAF-miR-296-3p-RAD18 signaling network in pancreatic and thyroid cancer cells, which leads to enhanced radioresistance.

and Relevance: Our analysis indeed confirms that BRAF mutation is associated with poor survival outcomes after liver resection of CRC metastases. However, upon quantitatively assessing the survival benefit of surgical intervention in patients with BRAF-mutated CRC liver metastases, we identified a significant 56% reduction in the risk of death.

The obtained results require validation on a larger group of patients. If the results are confirmed, the indicated lncRNAs may play an important role as diagnostic and prognostic markers.

P=N/A, N=80, Recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2026 --> Jul 2029 | Trial primary completion date: Dec 2026 --> Jul 2029

The results illustrate the mutation frequencies of KRAS, NRAS, BRAF genes and MSI status in stage I-III CRC from the eastern region of China. These findings further validate the associations between these genes status and various clinicopathological characteristics.

No abstract available

P1/2, N=113, Active, not recruiting, Fore Biotherapeutics | Trial completion date: Apr 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> May 2024

P3, N=569, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Aug 2024