Article
Oncology
Shaheer Khan, Sapna P. Patel, Alexander N. Shoushtari, Grazia Ambrosini, Serge Cremers, Shing Lee, Lauren Franks, Shahnaz Singh-Kandah, Susana Hernandez, Naomi Sender, Kristina Vuolo, Alexandra Nesson, Prabhjot Mundi, Benjamin Izar, Gary K. Schwartz, Richard D. Carvajal
Summary: The study tested the intermittent dosing schedule of selumetinib in patients with metastatic uveal melanoma. The results showed an increased maximum tolerated dose but no significant clinical efficacy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Sathya Neelature Sriramareddy, Fernanda Faiao-Flores, Michael F. Emmons, Biswarup Saha, Srikumar Chellappan, Clayton Wyatt, Inna Smalley, Jonathan D. Licht, Michael A. Durante, J. William Harbour, Keiran S. M. Smalley
Summary: This study investigates the role of HDAC11 in uveal melanoma and finds that it plays a crucial role in therapy adaptation by modulating the YAP/TAZ signaling pathway, leading to the escape of MEKi therapy.
CANCER GENE THERAPY
(2022)
Article
Oncology
Tyler D. Hitchman, Gabriella Bayshtok, Emilie Ceraudo, Amanda R. Moore, Cindy Lee, Ruobing Jia, Naitao Wang, Mohini R. Pachai, Alexander N. Shoushtari, Jasmine H. Francis, Youxin Guan, Juliet Chen, Matthew T. Chang, Barry S. Taylor, Thomas P. Sakmar, Thomas Huber, Ping Chi, Yu Chen
Summary: The study found that the combination of Gα(q) and MEK inhibition showed promising therapeutic potential in treating melanoma, suggesting an improved therapeutic strategy for targeting Gα(q) in uveal melanoma.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Svenja Mergener, Jens T. Siveke, Samuel Pena-Llopis
Summary: The study found that monosomy of chromosome 3 (M3) and mutations in BAP1 are associated with higher resistance to MEK inhibitors in uveal melanoma. Reconstitution of BAP1 was unable to restore sensitivity to MEK inhibition. Comparison of UM tumors with mutations in BAP1 and wild-type BAP1 from TCGA showed clear differentiation in overall and progression-free survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Oncology
Sathya Neelature Sriramareddy, Keiran S. M. Smalley
Summary: Most uveal melanomas have mutations in G alpha q and show constitutive MAPK activation. While MEK inhibition has limited efficacy, combining G alpha q inhibitor with MEK inhibitor can lead to prolonged suppression of MAPK signaling and improved therapeutic responses in preclinical uveal melanoma models.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Meredith S. Pelster, Stephen K. Gruschkus, Roland Bassett, Dan S. Gombos, Michael Shephard, Liberty Posada, Maura S. Glover, Rinata Simien, Adi Diab, Patrick Hwu, Brett W. Carter, Sapna P. Patel
Summary: The combination regimen of nivolumab plus ipilimumab shows activity in metastatic uveal melanoma, yielding deep and sustained confirmed responses.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Malcy Tarin, Fariba Nemati, Didier Decaudin, Christine Canbezdi, Benjamin Marande, Lisseth Silva, Heloise Derrien, Aart G. Jochemsen, Sophie Gardrat, Sophie Piperno-Neumann, Manuel Rodrigues, Pascale Mariani, Nathalie Cassoux, Marc-Henri Stern, Sergio Roman-Roman, Samar Alsafadi
Summary: Uveal Melanoma (UM) is a rare and malignant intraocular tumor with a poor prognosis. Despite efficient control of the primary tumor, up to 50% of patients develop metastases, mainly in the liver. Inhibitors targeting PKC and MEK have shown limited effectiveness, but the dual inhibition of FAK and MEK, as well as the combination of FAK and PKC inhibitors, hold promise as therapeutic interventions for metastatic UM.
Article
Oncology
Justine S. Paradis, Monica Acosta, Robert Saddawi-Konefka, Ayush Kishore, Frederico Gomes, Nadia Arang, Manoela Tiago, Silvia Coma, Simone Lubrano, Xingyu Wu, Kyle Ford, Chi-Ping Day, Glenn Merlino, Prashant Mali, Jonathan A. Pachter, Takami Sato, Andrew E. Aplin, J. Silvio Gutkind
Summary: Uveal melanoma is a common eye cancer with a high risk of developing metastatic uveal melanoma in the liver. The study has identified FAK and MEK-ERK co-targeting as a potential new precision therapeutic strategy for mUM, showing synergistic growth-inhibitory effects in vitro and in vivo models.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Ezekiel Weis, Jing Jiang, Alison H. Skalet, Carol L. Shields, R. Trafford Crump
Summary: The psychometric properties of a new patient-reported outcome instrument for uveal melanoma patients who have undergone brachytherapy were evaluated using classical test theory and item response theory. A cross-sectional study with a convenience sample of 439 participants from ocular oncology treatment centers identified three domains: Symptom Impairment, Worry, and Discomfort. The instrument showed good acceptability, reliability, and discrimination, making it suitable for post-treatment management.
Article
Oncology
Mark K. Doherty, Vincent C. Tam, Mairead G. McNamara, Raymond Jang, David Hedley, Eric Chen, Neesha Dhani, Patricia Tang, Hao-Wen Sim, Grainne M. O'Kane, Stephanie DeLuca, Lisa Wang, Theresa Pedutem, Jennifer J. Knox
Summary: The addition of sequential or continuous selumetinib to cisplatin and gemcitabine failed to improve efficacy and increased toxicity in patients with advanced biliary tract cancer.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Sebastian Bauer, James Larkin, F. Stephen Hodi, Frank Stephen, Ellen H. W. Kapiteijn, Gary K. K. Schwartz, Emilano Calvo, Padmaja Yerramilli-Rao, Sophie Piperno-Neumann, Richard D. D. Carvajal
Summary: The combination of PKC inhibitor sotrastaurin and MEK inhibitor binimetinib causes substantial gastrointestinal toxicity in patients with metastatic uveal melanoma, but stable disease is observed in a significant proportion of patients.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Hongjun Zhang, Xiangnan Liu, Yong'an Chen, Rui Xu, Shengli He
Summary: This study aimed to overcome the resistance of uveal melanoma (UM) to MEK inhibitors by targeting the epigenetic kinase. The results showed that KDOAM-25 inhibited the viability and colony formation, and promoted cell death of MEK-resistance cell lines through the regulation of H3K4me3 and H3K27ac. This suggests that KDOAM-25 may be a potential therapeutic agent for MEK resistance in UM patients.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Pharmacology & Pharmacy
Aml Mekkawy, Youssef W. Naguib, Suhaila O. Alhaj-Suliman, Emad Wafa, Kareem Ebeid, Timothy Acri, Aliasger K. Salem
Summary: The study explores the efficacy of a combination therapy of PTX and PD98059 in enhancing cytotoxicity against melanoma cells expressing the BRAF mutation. The use of PD98059-loaded NPs showed superior cellular uptake and cytotoxicity compared to soluble PD98059, suggesting a potential therapeutic approach for improving survival outcomes in patients with metastatic melanoma.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Oncology
Eric Pujade-Lauraine, Keiichi Fujiwara, Jonathan A. Ledermann, Amit M. Oza, Rebecca Kristeleit, Isabelle-Laure Ray-Coquard, Gary E. Richardson, Cristiana Sessa, Kan Yonemori, Susana Banerjee, Alexandra Leary, Anna Tinker, Kyung Hae Jung, Radoslaw Madry, Sang-Yoon Park, Charles K. Anderson, Fabian Zohren, Ross A. Stewart, Caimiao Wei, Samuel S. Dychter, Bradley J. Monk
Summary: This study compared the efficacy of avelumab alone, avelumab plus PLD, and PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer. The results showed that neither avelumab plus PLD nor avelumab alone significantly improved progression-free survival or overall survival compared to PLD.
Article
Surgery
Stephanie A. Blankenstein, Maartje W. Rohaan, Willem Martin C. Klop, Bernies van der Hiel, Bart A. van de Wiel, Max J. Lahaye, Sandra Adriaansz, Karolina Sikorska, Harm van Tinteren, Aysegul Sari, Lindsay G. Grijpink-Ongering, Winan J. van Houdt, Michel W. J. M. Wouters, Christian U. Blank, Sofie Wilgenhof, Johannes V. van Thienen, Alexander C. J. van Akkooi, John B. A. G. Haanen
Summary: This study evaluated the efficacy of neoadjuvant therapy with dabrafenib plus trametinib in enabling radical surgical resection in patients with unresectable locally advanced melanoma. The results showed that this treatment approach successfully allowed for radical resection in a significant proportion of patients with previously unresectable melanoma.