Background: Uveal melanoma is a rare cancer, in which metastases occur in approximately one half of cases. In metastatic disease, the prognosis is unfavorable and the median of survival does not exceed 6 months. Effective treatment options were very limited up to date. Tebentafusp is a bispecific fusion protein, which as the first drug proved efficacy in uveal melanoma.
Case: The patient was referred for suspected uveal melanoma of the left eye. She was treated for Hodgkin's disease in the past. Primarily, the tumor was treated by radiosurgery with radiotherapy of a small lesion of the vertebral body. However, later the patient had to undergo bulbus enucleation with confirmation of a large tumor category pT4b. PET/CT revealed metastases of the bones and the liver; simultaneously, haplotype A*02: 01 was confirmed. The patient underwent radiotherapy of the sternum and later, after confirmation of payment from the health insurance company, she started treatment with tebentafusp. The first three doses were administered during admission to the hospital, with a need to treat cytokine release syndrome by corticosteroids. Later, the administration was performed in an out-patient regimen, without complications, except for a transient elevation of transaminases. The first CT restaging confirmed stable disease; however, the second restaging confirmed a new osteolytic lesion in the processus of Th11. Because of progression, the treatment with tebentafusp was withdrawn after 6 months. Unfortunately, the lesion could not be treated by radiotherapy. Two months later, the patient was urgently admitted to the hospital because of right-sided hemiplegia; MRI revealed bleeding metastatic lesion in the brain stem.
Conclusion: In this case report, we present the case of the first patient treated with this drug in the Czech Republic.
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http://dx.doi.org/10.48095/ccko2024134 | DOI Listing |
Acta Pharm Sin B
December 2024
Department of Ophthalmology, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear.
View Article and Find Full Text PDFCancer Res Commun
January 2025
University of British Columbia, Vancouver, BC, Canada.
NF1 encodes the multifunctional tumour suppressor protein, neurofibromin, which is best known for its causative role in Neurofibromatosis type 1 and in regulating MAPK signaling. Neurofibromin, in a context-specific manner, is involved in various tumorigenic processes, including those in melanocytes. This study investigated whether NF1 loss can collaborate with oncogenic GNAQ to promote melanoma in the dermis or eyes, where the G alpha q pathway is almost always activated.
View Article and Find Full Text PDFJ Med Chem
January 2025
Foghorn Therapeutics, 500 Technology Square, Suite 700, Cambridge, Massachusetts 02139, United States.
BRM (SMARCA2) and BRG1 (SMARCA4) are mutually exclusive ATPase subunits of the mSWI/SNF (BAF) chromatin remodeling complex. BAF is an attractive therapeutic target because of its role in transcription, and mutations in the subunits of BAF are common in cancer and neurological disorders. Herein, we report the discovery of compound () as a potent allosteric inhibitor of the dual ATPase subunits from a high-throughput screening hit with a BRM IC of ∼27 μM.
View Article and Find Full Text PDFRadiat Oncol
January 2025
The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730000, China.
Background: Proton beam therapy (PBT) has been gradually introduced for treating choroidal melanoma. This study systematically reviewed clinical reports to evaluate the efficacy and safety of PBT in choroidal melanoma patients.
Methods: This systematic review included all the primary studies involving PBT for choroidal melanoma patients through April 2024.
Eye (Lond)
January 2025
Department of Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Objectives: This systematic review is aimed to evaluate the efficacy and safety of robotic Cyberknife radiotherapy (CKRT) in the treatment of uveal melanoma (UM).
Methods: Clinical studies published in English that assessed the efficacy and safety of robotic CKRT in UM were systematically searched in PubMed, Web of Science, Cochrane and Embase from inception to July 2023. Studies reporting extraocular tumours or other radiosurgery approaches were excluded.
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