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Immune checkpoint inhibitors have improved the treatment of many cancers. However, immune-related (IR) adverse events can limit their use. A rare but potentially severe IR adverse event is IR-cholangitis, which is mostly induced by anti-programmed cell death 1 (PD1) antibodies and is often corticosteroid-resistant.
View Article and Find Full Text PDFThe role of triple therapy and therapy sequence in treatment of BRAF-mutant metastatic melanoma. Response to overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study.
J Transl Med
August 2023
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Novel therapies have achieved unprecedented benefit in survival of advanced melanoma patients. While immunotherapy (ICI) can be administered independent of mutational status, BRAF and MEK kinase inhibitors represent another effective treatment option for patients with BRAF mutant melanoma. Given the benefits these therapies demonstrate, the natural instinct was to combine.
View Article and Find Full Text PDF[Vogt-Koyanagi-Harada syndrome in the setting of vemurafenib therapy for metastatic melanoma: a case report].
Zhonghua Yan Ke Za Zhi
November 2022
Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Beijing 100191, China.
A 53-year-old female patient complained of 1 week of bilateral visual blurring. She was previously diagnosed with metastatic melanoma of the inguinal lymph nodes and treated with the oral targeted drug vemurafenib. She exhibited aqueous flare in the left eye, and her fundus examination revealed optic disc swelling in the left eye and bilateral serious detachment of the retinal neuroepithelial layer.
View Article and Find Full Text PDFCombination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule.
View Article and Find Full Text PDFThe positive correlation between drug addiction and drug dosage in vemurafenib-resistant melanoma cells is underpinned by activation of ERK1/2-FRA-1 pathway.
Anticancer Drugs
November 2020
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostic, Institute of Aging Research, Guangdong Medical University, Dongguan.
Malignant melanoma is a kind of highly invasive and deadly diseases. The BRAF inhibitor (BRAFi) such as vemurafenib could achieve a high response rate in melanoma patients with BRAF mutation. However, melanoma cells could easily develop resistance as well as addiction to BRAFi.
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