BRAF wild-type

Interestingly, among patients with PTC with lymph node metastasis (LNM), right-side-affected LNM was significantly more common than left-side-affected LNM, which implies a biased regional LNM of right-side-located thyroid nodules (p = 0.0007). The size of BRAF-V600E mutated or right-lobe located nodules was significantly larger than that in the control group (p = 0.0156), and patients with a BRAF V600E mutation were considerably younger than those with wild-type BRAF.

Brain metastasis has a negative impact on long-term survival in BRAF-mutated, but not in BRAF-wildtype patients. Investigation of molecular features of brain metastases in BRAF-mutated vs. BRAF-wildtype melanomas may lead to new insights in tumor biology and may yield new therapeutic approaches.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jan 2026

P2, N=80, Terminated, AGITG | Active, not recruiting --> Terminated

The therapeutic EVs we constructed are effective and specific for the BRAFV600E-mutant CRC. This study provides a novel strategy for the treatment of CRC patients with BRAFV600E mutation.

P1/2, N=140, Recruiting, TiumBio Co., Ltd. | Phase classification: P1b/2a --> P1/2

Further, we have discussed dysregulated pathways associated with mutation of BRAFV600E, which includes MAPK/ERK, PI3K/AKT/mTOR, TP53, DNA damage response, and WNT/β-Catenin from schematic representation. In the current review, we have shown how these dysregulated pathways play pivotal roles in tumorigenesis, tumor progression in BRAF-mutant cancers and highlighted the critical role of BRAF dysregulation in cancer development followed by its therapeutic implications of targeting dysregulated pathways in BRAF-driven malignancies.

We experienced a case of cecal cancer with peritoneal dissemination accompanied by signet ring cell carcinoma, where maintenance chemotherapy proved effective.

These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases.

Patients with MSI-H CRC treated with ICIs exhibited similar outcomes regardless of germline or somatic MMR mutations. However, the presence of a BRAF V600E mutation was associated with a worse prognosis.

P1, N=42, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended

Overall, our findings suggest a complex interplay between sex and BRAF mutational status that may modulate the activity of ICIs in patients with MSI-H mCRC and pave the way to novel tailored strategies.

RAIR-DTC patients with BRAFV600E mutation treated with apatinib, donafenib, or anlotinib achieved better prognoses compared with patients with wild-type BRAF, indicating that the genetic background may play a role in predicting the efficacy of MKIs therapies.

While sorafenib demonstrates strong activity against wild-type B-Raf, it fails to effectively inhibit the mutated form of B-Raf...Additionally, it induced G2/M phase arrest and triggered dose-dependent apoptosis, effectively suppressing both cell proliferation and survival. Compound 9a also exhibited high selectivity for Raf isoforms with minimal off-target effects, underscoring its specificity and therapeutic potential for Raf-driven malignancies.

AI models may perform relatively well in predicting BRAF alterations in LGG using imaging data and appear to be capable of high sensitivities and specificities. However, future studies with larger sample sizes implementing different ML or DL algorithms are required to reduce imprecision.

CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance...The two groups achieved similar median PFS (mPFS) and median OS (mOS), with mPFS of 18 months and 12 months, respectively (P = 0.23), and mOS of 33 months and 20 months, respectively (P = 0.21), with no statistically significant differences. The results of this study demonstrated that CAPEOX combined with cetuximab is an equally viable option for first-line treatment of RAS/BRAF wild-type mCRC as FOLFOX combined with cetuximab.

P1/2, N=30, Not yet recruiting, Brown University | Trial primary completion date: Jan 2025 --> Mar 2026

Immunopositivity for pMEK1/2 in most suggests a scope for MEK1-targeted therapy in recalcitrant PTC cases even in the absence of the BRAF mutation. In addition, IHC is a reliable technique for detecting BRAF V600E mutation but needs validation by correlation with molecular studies.

P1, N=39, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

P2, N=169, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jan 2026

P2, N=38, Recruiting, Sun Yat-Sen University Cancer Center; Sun Yat-Sen University Cancer Center | Not yet recruiting --> Recruiting

Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results.

Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAFwt/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells.

These findings suggest that tumorigenesis and mutational processes differ based on tumor sidedness. Further studies are needed to substantiate these findings.

These findings support the use of bevacizumab-based over aflibercept-based regimens as II-line treatment in mCRC, especially in KRAS/NRAS and BRAF wild type tumors.

P1, N=232, Active, not recruiting, Genentech, Inc. | Trial completion date: May 2025 --> Mar 2026 | Trial primary completion date: May 2025 --> Mar 2026 | Recruiting --> Active, not recruiting

We also demonstrate that melanocyte-specific knockout of PTPN23 significantly inhibits BRAFV600E-driven melanomagenesis. Altogether, our findings demonstrate that targeting PTPN23/PI3KC2α offers a new and viable therapeutic strategy for BRAF-mutant cancers.

This exploratory analysis from a randomized phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to peri-operative FOLFOX in RAS/BRAF-wt LACC. Hyperselection with EREG/AREG status was associated with increased efficacy. A dedicated prospective trial within a biomarker selected population is under development.

A multivariate analysis revealed that postresection anti-EGFR mAb was an independent predictor of prolonged OS. In conclusion, for mCRC patients who have undergone secondary resection after first-line anti-EGFR mAb plus doublet chemotherapy, continuing anti-EGFR mAb may significantly extend OS, regardless of the primary tumor location.

Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.

The patient underwent six cycles of chemotherapy with FOLFOX (oxaliplatin in combination with 5-fluorouracil and leucovorin), and radiofrequency ablation (RFA) was applied to the lesion in segment VI, resulting in a favorable response in imaging control. In addition to the dissection and section of the middle and left hepatic vein included in the surgical specimen. The patient experienced a rapid postoperative recovery with good liver function, an early hospital discharge, and a quick return to work, highlighting the clear advantages of laparoscopic surgery.

Our study demonstrates that pMLH1 hypermethylation, MMRd, BRAFmut and CIMP phenotype do not completely overlap in CRC. These findings further refine the knowledge on the molecular landscape of CRC and may have critical implications also for the clinical management of the disease.

The MOUNTAINEER-03 phase III trial is designed to investigate the efficacy and safety of first-line tucatinib in combination with trastuzumab and modified FOLFOX6 (mFOLFOX6) versus standard of care (mFOLFOX6 plus bevacizumab or cetuximab) in patients with untreated HER2+, RAS WT locally advanced unresectable or mCRC...Key secondary endpoints are overall survival and confirmed objective response rate (according to RECIST v1.1 per BICR). Safety assessments will include surveillance and recording of adverse events, physical examination findings, vital signs, cardiac assessments, Eastern Cooperative Oncology Group performance status, concomitant medications, and laboratory tests.Clinical trial registration: NCT05253651 (ClinicalTrials.gov).

A 55-year-old woman with Stage IIIb cutaneous melanoma, receiving adjuvant therapy with anti-PD-1, after seven cycles of pembrolizumab, developed mediastinal node enlargement and skin hypodermic nodes...A 48-year-old woman with Stage IIIb BRAF wild-type melanoma, receiving nivolumab every 4 weeks, developed systemic sarcoidosis after seven cycles, primarily affecting extrapulmonary sites...A 65-year-old man with Stage IIIb BRAF-mutant melanoma, receiving dabrafenib and trametinib, developed lung and cutaneous sarcoidosis, presenting with symptoms that led to emergency department admission. In all cases, the MDT played a crucial role in determining the course of treatment and balancing the risks of continuing or suspending cancer therapies while managing SLRs. National and international guidelines were consulted, but tailored decisions by the MDT were essential for optimizing patient care.

P3, N=508, Recruiting, Fudan University | N=386 --> 508 | Trial completion date: Dec 2026 --> Sep 2027 | Trial primary completion date: Dec 2023 --> Mar 2025

Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

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

Triplet induction chemotherapy is a treatment of choice in selected patients with SMRC, allowing to adapt the therapeutic strategy to the response and invasiveness of the various sites.

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. Those patients also achieved a significantly greater disease control rate (89% vs 20%; P = 0.008). In conclusion, LB evaluating ctDNA is informative and may help to guide treatment in patients with BRAF V600E-mutated mCRC.

P2, N=3, Terminated, Jonsson Comprehensive Cancer Center | N=28 --> 3 | Trial completion date: Jun 2026 --> Nov 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Nov 2024; poor enrollment

In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model, as well as other relevant anemia models. This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias, including DBA.