Knockdown of 15-bp Deletion-Type v-raf Murine Sarcoma Viral Oncogene Homolog B1 mRNA in Pancreatic Ductal Adenocarcinoma Cells Repressed Cell Growth In Vitro and Tumor Volume In Vivo

Song, Jiaxuan; Kobayashi, Yoshito; Asano, Yoshimasa; Sato, Atsushi; Taniguchi, Hiroaki; Ui-Tei, Kumiko

doi:10.3390/cancers14133162

Cited by 2 publications

(1 citation statement)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The L485-P490 deletion mutation was first detected in the cell lines of the pancreatic, lung, and ovarian cancers, which is a novel BRAF in-frame deletion near the αC-helix region of the kinase domain and functions as a BRAF homodimer. Because the deletion and these Frontiers in Pharmacology frontiersin.org mutant signals act as active dimers, L485-P490 deletion mutation was classified as a class II BRAF mutation (Yaeger and Corcoran, 2019;Song et al, 2022). In addition, the MAPK activation mediated by L485-P490 deletion mutation was resistant to RAF monomer inhibitors, such as vemurafenib, but sensitive to an RAF dimer inhibitor (Chen et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

BRAF L485–P490 deletion mutant metastatic melanoma sensitive to BRAF and MEK inhibition: A case report and literature review

et al. 2023

View full text Add to dashboard Cite

Background: The combination therapy of BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been approved as a first-line treatment for metastatic melanoma with BRAF V600 mutants. Recently, BRAF mutations have been divided into three subtypes based on biochemical and signaling characteristics. Unlike V600 mutants that show class I BRAF mutations, evidence of the effects of using BRAF inhibitors and MEK inhibitors in patients with non-V600 BRAF mutations remains unclear. The exploration of effective therapy for non-V600 BRAF mutations in melanoma has thus attracted much interest.Case presentation: We reported a case of a 64-year-old female metastatic melanoma patient with a novel BRAF p.L485–P490 deletion mutation. The patient received anti-PD1 agent pembrolizumab (100 mg) therapy as the first-line treatment for two cycles, which was terminated due to an intolerable adverse effect. Considering the p.L485–P490 deletion mutation signal as an active dimer which is akin to a class II BRAF mutation, the patient underwent dabrafenib and trametinib combination therapy as a second-line treatment. After two cycles of combination treatment, the patient achieved a partial response confirmed by radiological examinations. At the last follow-up date, the patient had obtained over 18 months of progression-free survival, and the treatment was well tolerated.Conclusion: The combination therapy of dabrafenib and trametinib has been proven to be an effective method as a later-line therapy for metastatic melanoma patients with class II BRAF in-frame deletion mutations.

show abstract

Section: Discussionmentioning

confidence: 99%