Article
Oncology
Hussein Akil, Mercedes Quintana, Jeremy H. Raymond, Tommy Billoux, Valentin Benboubker, Sophie Besse, Philippe Auzeloux, Veronique Delmas, Valerie Petit, Lionel Larue, Michel D'Incan, Francoise Degoul, Jacques Rouanet
Summary: Targeted radionuclide therapy (TRT) combined with MAPK/ERK inhibitors shows additive efficiency in BRAF and NRAS mutant melanoma cells. TRT has a significant therapeutic effect on NRAS(Q61K) mutated melanoma and reduces metastasis capacity.
Article
Oncology
Weijia Cai, Mai Q. Nguyen, Nicole A. Wilski, Timothy J. Purwin, Megane Vernon, Manoela Tiago, Andrew E. Aplin
Summary: In this study, it was demonstrated that loss of phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi, and the synergistic effects of PDPK1 loss and MEKi were validated in NRAS mutant melanoma cell lines.
Article
Biochemistry & Molecular Biology
Rita Casadonte, Mark Kriegsmann, Katharina Kriegsmann, Helene Streit, Rolf Ruediger Meliss, Cornelia S. L. Mueller, Joerg Kriegsmann
Summary: This study used proteomic technology to compare the molecular profiles of BRAF and NRAS mutated and wildtype melanoma patients' tissue samples. The results showed molecular differences between BRAF and NRAS mutated melanoma, and accurate identification was possible with an accuracy of 87-89% and 76-79% depending on the classification method.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Filippo de Braud, Christophe Dooms, Rebecca S. Heist, Celeste Lebbe, Martin Wermke, Anas Gazzah, Dirk Schadendorf, Piotr Rutkowski, Juergen Wolf, Paolo A. Ascierto, Ignacio Gil-Bazo, Shumei Kato, Maria Wolodarski, Meredith McKean, Eva Munoz Couselo, Martin Sebastian, Armando Santoro, Vesselina Cooke, Luca Manganelli, Kitty Wan, Anil Gaur, Jaeyeon Kim, Giordano Caponigro, Xuan-Mai Couillebault, Helen Evans, Catarina D. Campbell, Sumit Basu, Michele Moschetta, Adil Daud
Summary: This study explores a targeted therapy for treating NRAS-mutant melanoma, showing promising antitumor activity in patients with the use of LXH254 and trametinib in combination.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexandra Landras, Coralie Reger de Moura, Bruno O. Villoutreix, Maxime Battistella, Aurelie Sadoux, Nicolas Dumaz, Suzanne Menashi, Juan Fernandez-Recio, Celeste Lebbe, Samia Mourah
Summary: CD147i, a specific inhibitor of CD147/VEGFR-2 interaction, shows potential therapeutic effects for NRAS(mut) melanoma cells. It significantly inhibits malignant properties of melanoma and exhibits synergy with MEKi.
Article
Oncology
Lisa Dinter, Paula C. Karitzky, Alexander Schulz, Alexander A. Wurm, Marie-Christin Mehnert, Mildred Sergon, Antje Tunger, Mathias Lesche, Rebekka Wehner, Anja Mueller, Theresa Kaeubler, Heike Niessner, Andreas Dahl, Stefan Beissert, Marc Schmitz, Friedegund Meier, Barbara Seliger, Dana Westphal
Summary: This study investigated the combined effects of MEK inhibitors (MEKi) and BRAF inhibitors (BRAFi) on sensitive NRAS-mutant melanoma cells, including their ability to inhibit proliferation, induce apoptosis, and alter the expression of immune modulatory molecules. The study found that BRAFi significantly enhanced the antiproliferative and proapoptotic activity of MEKi, and upregulated the expression of immune relevant molecules in melanoma cells.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Dermatology
Samantha M. Guhan, Michael Shaughnessy, Anpuchchelvi Rajadurai, Michael Taylor, Raj Kumar, Zhenyu Ji, Sarem Rashid, Keith Flaherty, Hensin Tsao
Summary: Targeting transcriptional dependencies through selective inhibition of CDK9 is an effective method for suppressing therapeutically orphaned BRAF/NRAS/NF1 wild-type melanomas.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Oncology
Gabriella Liszkay, Zoltan Matrai, Kata Czirbesz, Nora Jani, Eszter Bencze, Istvan Kenessey
Summary: The study found that Breslow thickness was a risk factor for SLN positivity in melanoma patients, while the NRAS mutant subgroup showed poorer progression-free and distant metastasis-free survival rates. Despite the relatively lower SLN positivity rate in NRAS-mutant patients, closer monitoring for disease progression is still necessary.
Article
Toxicology
Sowjanya Thatikonda, Venkatesh Pooladanda, Ramya Tokala, Shankaraiah Nagula, Chandraiah Godugu
Summary: Malignant melanoma, a deadly aggressive form of skin cancer, frequently metastasizes to distal organs and is associated with BRAF or NRAS mutations in 30 to 50% of patients. Niclosamide, an FDA-approved anthelmintic drug, has shown strong anticancer properties against various tumors. In this study, the researchers investigated the role of Niclosamide in inhibiting metastatic melanoma in vitro using SK-MEL-2 and SK-MEL-28 cell lines. They found that Niclosamide induces apoptosis and ROS generation, inhibits cell cycle progression, and suppresses metastasis. Furthermore, Niclosamide inhibits key markers involved in the EMT signaling cascade. These findings provide valuable insights into the mechanism of Niclosamide in BRAF/NRAS mutant melanoma cells and its potential as a therapeutic agent.
TOXICOLOGY IN VITRO
(2023)
Article
Chemistry, Medicinal
Xiu-Cai Chen, Gui-Xue Tang, Jing Dai, Le-Tian Dai, Tian-Ying Wu, Wen-Wei Li, Tian-Miao Ou, Zhi-Shu Huang, Jia-Heng Tan, Shuo-Bin Chen
Summary: Mutations in NRAS contribute to tumor formation and resistance to drugs. The development of novel strategies to suppress NRAS for anticancer therapy is urgent, as this protein is usually considered untargetable. Recent research has shown that a G-quadruplex structure in the untranslated region of NRAS mRNA can reduce NRAS translation, providing a potential NRAS suppression strategy. In this study, a cell-based screening method was developed using a G-quadruplex-triggered fluorogenic hybridization probe, and the clinically used agent Octenidine was identified as a potent NRAS repressor. Octenidine inhibited NRAS translation, blocked MAPK and PI3K-AKT signaling, and induced cell cycle arrest, apoptosis, and autophagy. It exhibited better antiproliferative effects compared to clinical antimelanoma agents and could inhibit the growth of NRAS-mutant melanoma in a mouse model. These results suggest that Octenidine may be a promising therapy for NRAS-mutant melanoma.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Tijana Randic, Ines Kozar, Christiane Margue, Jochen Utikal, Stephanie Kreis
Summary: Genetic alterations affecting RAS proteins are common in human cancers, with NRAS mutations posing challenges in melanoma treatment. Despite advancements in targeted and immunotherapies, patients with NRAS(mut) melanomas have poorer prognosis due to aggressive tumors and lack of effective treatments. Understanding therapy resistance mechanisms and exploring novel approaches are crucial for improving outcomes in this patient group.
CANCER TREATMENT REVIEWS
(2021)
Article
Oncology
Angelika Bickel, Stefan Diem, Lukas Flatz, Bjorn Stinn, Marco Siano
Summary: Standard treatment for advanced melanoma, including dacarbazine and interleukin-2, has low response rates and significant toxicity. New treatments such as immunotherapy and targeted therapy for patients with a BRAF mutation have shown promise, but options for patients with a NRAS mutation are limited.
JOURNAL OF CANCER RESEARCH AND THERAPEUTICS
(2021)
Article
Medicine, Research & Experimental
Ester Simeone, Giosue Scognamiglio, Mariaelena Capone, Diana Giannarelli, Antonio M. Grimaldi, Domenico Mallardo, Gabriele Madonna, Marcello Curvietto, Assunta Esposito, Fabio Sandomenico, Francesco Sabbatino, Nicholas L. Bayless, Sarah Warren, SuFey Ong, Gerardo Botti, Keith T. Flaherty, Soldano Ferrone, Paolo A. Ascierto
Summary: Studies have shown that the combination of vemurafenib and IFN-alpha may benefit patients with BRAFV600E melanoma, with IFNAR1 expression levels correlating with treatment response and survival. The vemurafenib + PEG-IFN-alpha-2b + cobimetinib combination showed overall safety, but may face challenges in finding a niche in current treatment scenarios for advanced melanoma.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Emilio Francesco Giunta, Vincenzo De Falco, Pietro Paolo Vitiello, Luigi Pio Guerrera, Gabriella Suarato, Rossella Napolitano, Alessandra Perrone, Giuseppe Argenziano, Renato Franco, Michele Caraglia, Erika Martinelli, Davide Ciardiello, Fortunato Ciardiello, Stefania Napolitano, Teresa Troiani
Summary: Liquid biopsy, using real-time quantitative PCR, is useful for melanoma diagnosis and treatment monitoring, especially in high disease burden patients. However, the low sensitivity of this technique may not be sufficient for predicting relapses in radically resected patients.
Article
Cell Biology
Emilie Jaune, Elisa Cavazza, Cyril Ronco, Oleksandr Grytsai, Patricia Abbe, Nedra Tekaya, Marwa Zerhouni, Guillaume Beranger, Lisa Kaminski, Frederic Bost, Maeva Gesson, Meri Tulic, Paul Hofman, Robert Ballotti, Thierry Passeron, Thomas Botton, Rachid Benhida, Stephane Rocchi
Summary: The compound CRO15 shows promising anti-melanoma effects by acting on melanoma cells through two distinct mechanisms, leading to cell death. This compound has potential in reducing the growth of melanoma xenografts sensitive or resistant to BRAF inhibitors.
CELL DEATH & DISEASE
(2021)