CREB3 overexpression contributed to Donafenib resistance in HCC cells by activating the ZFAS1/p65 axis.

Our findings reveal that BDE209 exacerbates MAPK activation, undermining dabrafenib's inhibitory effects by triggering the EGFR pathway, thereby highlighting BDE209's potential to diminish the pharmacological efficacy of dabrafenib in treating BRAF-mutated PTC. This research underscores the importance of considering environmental factors like BDE209 exposure in the effective management of thyroid carcinoma treatment strategies.

P2, N=33, Not yet recruiting, M.D. Anderson Cancer Center

P1, N=40, Recruiting, Peking Union Medical College Hospital

P3, N=470, Not yet recruiting, Erasca, Inc.

Overexpressing RUVBL1 enhanced the viability, wound healing percentage, invasion, sphere formation, angiogenesis, and resistance to cisplatin and 5-fluorouracil in CAL-27 and SCC-4 cells, and the opposite results were obtained by knocking down RUVBL1. In conclusion, RUVBL1 contributes to the malignant biological behavior of TSCC via activating the CRAF/MEK/ERK pathway. This provides molecular mechanisms and perspectives for targeted therapy of the CRAF/MEK/ERK pathway.

P1, N=27, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

This protocol describes the procedures for seeding, transfecting, and replating the cells, along with detailed instructions for reading BRET emissions, performing data analysis, and confirming protein expression levels. In addition, example assay results, along with optimization and troubleshooting steps, are provided.

Avutometinib, and to a larger extent its combination with FAK inhibitor VS-4718, demonstrated promising in vivo activity against a KRAS wild-type LGSOC-PDX. These data support the ongoing registration-directed study (RAMP201/NCT04625270).

P2, N=225, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting

P1, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | N=22 --> 30 | Trial completion date: Jun 2024 --> Jun 2025 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=119, Recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial primary completion date: Feb 2024 --> Sep 2024

Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.

P1, N=18, Active, not recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=5, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2027 --> Oct 2023 | Active, not recruiting --> Terminated; NCI decided to terminate ABTC Consortium due to NCI moving in different direction for Brain Cancer

In 52 cases, six cases (4 of SD cases and 2 of PR cases) was administered encorafenib-based chemotherapies based on BRAF gene mutation... Around 13% of gastrointestinal cancer patients with liver metastasis might have a druggable benefit by CGP testing. BRAF mutation might be promising target for patients with liver metastasis. ZNF217, SRC, ARFRP1, BARD1, FGF10 might be associated with metastatic process to liver in gastrointestinal cancer.

P3, N=922, Active, not recruiting, Pfizer | Trial completion date: Nov 2023 --> Mar 2024

The results from these clinical studies suggest that encorafenib does not cause clinically relevant CYP2B6 induction or inhibition but is an inhibitor of BCRP and may also inhibit OATP1B1/3 to a lesser extent. Based on these results, it may be necessary to consider switching statins or reducing statin dosage accordingly for coadministration with encorafenib.

P1/2, N=33, Recruiting, University of Utah | Not yet recruiting --> Recruiting

P1/2, N=153, Recruiting, Verastem, Inc. | N=53 --> 153 | Trial completion date: Sep 2025 --> Apr 2027

P1, N=27, Suspended, M.D. Anderson Cancer Center | Phase classification: P1b --> P1 | Not yet recruiting --> Suspended

P2, N=56, Completed, Guangxi Medical University

P2, N=38, Recruiting, Wuhan Union Hospital, China

These results support the use of encorafenib plus binimetinib combination treatment as a new treatment option in people with BRAF V600E-mutant metastatic NSCLC. The side effects of encorafenib plus binimetinib in this study were similar to the side effects seen with encorafenib plus binimetinib in people with a type of skin cancer called metastatic melanoma.

Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer.

P3, N=176, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

It was identified that top-hit molecules had better binding and interaction activity than standard in all three classes of mutants.

P1/2, N=130, Not yet recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd

P2, N=95, Completed, Pierre Fabre Medicament | Active, not recruiting --> Completed

P1/2, N=53, Recruiting, University of Chicago | Phase classification: P1b/2 --> P1/2

P2, N=6, Terminated, Academic and Community Cancer Research United | N=29 --> 6 | Trial completion date: Dec 2024 --> Nov 2023 | Active, not recruiting --> Terminated; Slow accrual

Finally, we confirmed sex-dependent tumor promoting effects of TS in a large cohort of LC patients. Our study highlights the sex-dependent genomic responses to TS and the interplay of circadian clock genes and hormone receptors in the regulation of oncogenes and oncomirs in LC growth.

P2, N=103, Active, not recruiting, Pierre Fabre Medicament | Trial primary completion date: Apr 2024 --> Dec 2023

P2, N=70, Not yet recruiting, Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

This activity is supported by educational grants from Natera Inc and Pfizer Inc. Similarities and differences between BRAF V600E and non-V600 mutations in mCRC; implications for disease management Potential clinical or biological factors, such as patient characteristics, tumor sidedness, histology and co-mutations, associated with the presence of BRAF V600 mutations in CRC Long-term findings from the Phase III BEACON CRC study evaluating encorafenib/cetuximab with or without binimetinib versus standard therapy for patients with mCRC and BRAF V600E mutations FDA approval and appropriate integration of encorafenib/cetuximab for patients with BRAF V600E-mutated mCRC Rationale for the evaluation of earlier use of BRAF-targeted therapy; findings from the Phase II ANCHOR CRC trial evaluating encorafenib/binimetinib/cetuximab for patients with treatment-naïve BRAF V600E-mutated mCRC Design, eligibility criteria and key endpoints of the Phase III BREAKWATER trial comparing encorafenib/cetuximab with or without chemotherapy to standard chemotherapy for patients with previously untreated BRAF V600E-mutated mCRC; safety lead-in results and estimated completion date

Our primary objective was to identify subgroups with different treatment responses using Latent Class Mixed Model (LCMM).We used a public dataset and focused on one treatment, encorafenib, and two indications, melanoma and colorectal cancer, for which efficacy depends on a specific mutation BRAF V600E...LCMM is a suitable tool for MCT to explore treatment response subgroups of PDX. Once these subgroups are defined, characterization of their phenotypes/genotypes could be performed to explore treatment response predictors.

No abstract available

P2, N=90, Completed, Verastem, Inc. | Recruiting --> Completed | Trial completion date: Dec 2025 --> Dec 2023 | Trial primary completion date: Mar 2023 --> Aug 2023

P2/3, N=156, Recruiting, Peking University | Trial primary completion date: Dec 2023 --> Jun 2024

Additionally, we emphasize the effect that CRAF alterations may have on drug resistance and how precision therapies could effectively target CRAF-dependent tumours. Here, we discuss preclinical and clinical findings that may lead to improved treatments for all types of oncogenic RAF1 alterations in cancer.

P1/2, N=33, Not yet recruiting, University of Utah

P1/2, N=78, Recruiting, Peter MacCallum Cancer Centre, Australia | Phase classification: P1b --> P1/2 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024