Article
Cell Biology
Joanna P. Wroblewska, Dora Dias-Santagata, Adam Ustaszewski, Cheng-Lin Wu, Masakazu Fujimoto, M. Angelica Selim, Wojciech Biernat, Janusz Rys, Andrzej Marszalek, Mai P. Hoang
Summary: The NRAS mutation is an independent predictor of worse survival in mucosal melanomas, while the significance of other related mutations remains unclear.
Review
Biology
Jiri Vachtenheim, Lubica Ondrusova
Summary: Advanced melanoma is difficult to cure, with resistant cells developing universally and requiring further drug therapy. Multiple mechanisms lead to the development of resistance, emphasizing the need for personalized treatment. Combined therapy may be an effective approach to reducing drug resistance.
Article
Oncology
Sophie Gardrat, Alexandre Houy, Kelly Brooks, Nathalie Cassoux, Raymond Barnhill, Stephane Dayot, Ivan Bieche, Virginie Raynal, Sylvain Baulande, Richard Marais, Sergio Roman-Roman, Marc-Henri Stern, Manuel Rodrigues
Summary: Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma that originates from partially sunlight-exposed mucosa. Through sequencing and studying its mutational landscape, we found different molecular subtypes of ConjMel with oncogenic drivers shared with mucosal and skin melanomas.
Article
Oncology
Anastasia Lyon, Rakshamani Tripathi, Christina Meeks, Daheng He, Yuanyuan Wu, Jinpeng Liu, Chi Wang, Jing Chen, Haining Zhu, Sujata Mukherjee, Saptadwipa Ganguly, Rina Plattner
Summary: Melanomas with NRAS mutations are aggressive and difficult to treat. In cases where immune checkpoint blockade is not effective, there are no good treatment options. However, targeting the RAF/MEK/ERK pathway can potentially improve survival. ABL1/2 and DDR1 have been identified as critical factors in MEK inhibitor resistance in NRAS-mutant melanomas.
Review
Medical Laboratory Technology
Scott C. Bresler, Caroline Simon, Carol L. Shields, Jonathan B. McHugh, Anna M. Stagner, Rajiv M. Patel
Summary: Conjunctival melanocytic lesions comprise a range of neoplastic and nonneoplastic conditions. Accurate histologic classification is crucial for diagnosing these lesions. This article provides an overview of different classification schemes and updates on molecular features and prognostic indicators.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Amanda S. Hirata, Paula Rezende-Teixeira, Joao Agostinho Machado-Neto, Paula C. Jimenez, James J. La Clair, William Fenical, Leticia V. Costa-Lotufo
Summary: Isolated from marine bacteria Serinicoccus sp., seriniquinone (SQ1) has selective activity in melanoma cell lines by modulating human dermcidin, inducing autophagy and apoptosis. The analogue SQ2 shows improved solubility and higher selectivity for melanoma cells. BRAF and NRAS mutations exhibit different sensitivities to autophagy inhibition when exposed to SQ1 and SQ2, suggesting potential treatment strategies for BRAF-mutated tumors.
Article
Oncology
Seungyeon Jung, Emma Armstrong, Alexander Z. Wei, Fei Ye, Aaron Lee, Matteo S. Carlino, Ryan J. Sullivan, Richard D. Carvajal, Alexander N. Shoushtari, Douglas B. Johnson
Summary: This multicenter study highlights KIT alterations that are sensitive to imatinib and further supports the use of imatinib in subsets of KIT-altered melanoma.
BRITISH JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Bardees M. Foda, Richard R. Neubig
Summary: This study introduces the first drug-resistant mouse melanoma models and reveals that resistance is driven by activation of Rho and the downstream transcriptional coactivator, MRTF. Inhibition of the Rho/MRTF pathway enhances sensitivity to drugs and co-treatment with inhibitors eliminates resistant colony development. The resistant cells grow slower in vitro but develop aggressive tumors in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jacob S. Choi, Sunandana Chandra
Summary: Targeted therapies have shown significant clinical activity in BRAF wild-type melanoma, especially in patients with poor response to ICIs. Next-generation immunotherapies may represent the latest breakthrough in the treatment of melanoma.
CURRENT ONCOLOGY REPORTS
(2022)
Article
Dentistry, Oral Surgery & Medicine
Tamara da Silva Vieira, Leticia Martins Guimaraes, Marina Goncalves Diniz, Bianca Gomes-Fernandes, Wilma Terezinha Anselmo-Lima, Edwin Tamashiro, Luciana Bastos-Rodrigues, Luiz De Marco, Ricardo Santiago Gomez, Fabiana Cardoso Pereira Valera, Carolina Cavalieri Gomes
Summary: This study suggests that pathogenic mutations in KRAS, BRAF, and EGFR genes are not frequent events in CRSwNP, and if they occur, they might represent marginal events at best.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2023)
Article
Oncology
Gregory J. Riely, Egbert F. Smit, Myung-Ju Ahn, Enriqueta Felip, Suresh S. Ramalingam, Anne Tsao, Melissa Johnson, Francesco Gelsomino, Raymond Esper, Ernest Nadal, Michael Offin, Mariano Provencio, Jeffrey Clarke, Maen Hussain, Gregory A. Otterson, Ibiayi Dagogo-Jack, Jonathan W. Goldman, Daniel Morgensztern, Ann Alcasid, Tiziana Usari, Paul Wissel, Keith Wilner, Nuzhat Pathan, Svitlana Tonkovyd, Bruce E. Johnson
Summary: The combination of encorafenib and binimetinib showed clinical efficacy and acceptable safety in patients with BRAF(V600E)-mutant metastatic NSCLC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
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
James M. Cleary, Victoria Wang, Rebecca S. Heist, E. Scott Kopetz, Edith P. Mitchell, James A. Zwiebel, Kevin S. Kapner, Helen X. Chen, Shuli Li, Robert J. Gray, Lisa M. McShane, Larry V. Rubinstein, David R. Patton, Funda Meric-Bernstam, Melissa S. Dillmon, P. Mickey Williams, Stanley R. Hamilton, Barbara A. Conley, Andrew J. Aguirre, Peter J. O'Dwyer, Lyndsay N. Harris, Carlos L. Arteaga, Alice P. Chen, Keith T. Flaherty
Summary: The study suggests that single-agent binimetinib did not show significant efficacy in NRAS-mutated cancers, but observed increased overall survival and progression-free survival in patients with NRAS codon 61-mutated colorectal cancer warrant further investigation.
CLINICAL CANCER RESEARCH
(2021)
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)
Article
Oncology
Xuejun Gao, Dandan Xue, Jingjing Cheng, Xin Zhang, Xia Cai
Summary: This study investigated the effect of Axl inhibitor on the PI3K/Akt pathway in NRAS-mutant melanoma cells and found that Axl inhibitor can synergistically promote the effect of Akt inhibitor, resulting in a stronger therapeutic effect on melanoma.
JOURNAL OF ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Daniel Abate-Daga, Maria C. Ramello, Inna Smalley, Peter A. Forsyth, Keiran S. M. Smalley
BIOCHEMICAL PHARMACOLOGY
(2018)
Letter
Oncology
Sarah Sloot, Yian A. Chen, Xiuhua Zhao, Jamie L. Weber, Jacob J. Benedict, James J. Mule, Keiran S. Smalley, Jeffrey S. Weber, Jonathan S. Zager, Peter A. Forsyth, Vernon K. Sondak, Geoffrey T. Gibney
Article
Oncology
Zeynep Eroglu, Y. Ann Chen, Geoffrey T. Gibney, Jeffrey S. Weber, Ragini R. Kudchadkar, Nikhil I. Khushalani, Joseph Markowitz, Andrew S. Brohl, Leticia F. Tetteh, Howida Ramadan, Gina Arnone, Jiannong Li, Xiuhua Zhao, Ritin Sharma, Lancia N. F. Darville, Bin Fang, Inna Smalley, Jane L. Messina, John M. Koomen, Vernon K. Sondak, Keiran S. M. Smalley
CLINICAL CANCER RESEARCH
(2018)
Editorial Material
Dermatology
Fernanda Faiao-Flores, Keiran S. M. Smalley
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2018)
Editorial Material
Oncology
Inna Smalley, Keiran S. M. Smalley
Editorial Material
Biology
Keiran S. M. Smalley
Article
Oncology
Jessica Goncalves, Michael F. Emmons, Fernanda Faiao-Flores, Andrew E. Aplin, J. William Harbour, Jonathan D. Licht, Marcia R. Wink, Keiran S. M. Smalley
PIGMENT CELL & MELANOMA RESEARCH
(2020)
Review
Oncology
Isabella C. Glitza, Keiran S. M. Smalley, Priscilla K. Brastianos, Michael A. Davies, Ian McCutcheon, James K. C. Liu, Kamran A. Ahmed, John A. Arrington, Brittany R. Evernden, Inna Smalley, Zeynep Eroglu, Nikhil Khushalani, Kim Margolin, Harriet Kluger, Michael B. Atkins, Hussein Tawbi, Adrienne Boire, Peter Forsyth
PIGMENT CELL & MELANOMA RESEARCH
(2020)
Article
Dermatology
Chao Zhang, Inna Smalley, Michael F. Emmons, Ritin Sharma, Victoria Izumi, Jane Messina, John M. Koomen, Elena B. Pasquale, Peter A. Forsyth, Keiran S. M. Smalley
Summary: The acquired BRAF inhibitor resistance in melanoma is associated with a new transcriptional state leading to increased metastatic risk, driven by noncanonical EphA2 signaling and mesenchymal-to-amoeboid transition. Histone deacetylase 8 activity is crucial for the drug-resistant metastatic state, affecting melanoma-endothelial cell interactions and tumor dissemination.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Review
Dermatology
Manali Phadke, Alpaslan Ozgun, Zeynep Eroglu, Keiran S. M. Smalley
Summary: The development of brain metastases is the deadliest complication of advanced melanoma, and recent progress has been made in therapies for melanoma brain metastases (MBM). However, there are lower response durations for intracranial metastases compared to extracranial metastases, possibly due to unique features of the brain microenvironment. Current research focuses on the biology and pathophysiology of melanoma brain metastasis development, as well as the challenges faced in clinical trials and treatment for MBM patients.
EXPERIMENTAL DERMATOLOGY
(2022)
Editorial Material
Oncology
Inna Smalley, Keiran S. M. Smalley
Summary: In this study, the authors used RNA sequencing and multiplexed IHC to analyze the spatial immune landscape of melanoma patients. They found that the spatial interaction between cytotoxic T cells and M1-like macrophages expressing PD-L1 can predict the response to immune checkpoint inhibition.
Editorial Material
Oncology
Keiran S. M. Smalley
CLINICAL CANCER RESEARCH
(2023)
Editorial Material
Oncology
Manali S. S. Phadke, Keiran S. M. Smalley
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Inna Smalley, Adrienne Boire, Priscilla Brastianos, Harriet M. Kluger, Eva Hernando-Monge, Peter A. Forsyth, Kamran A. Ahmed, Keiran S. M. Smalley, Sherise Ferguson, Michael A. Davies, Isabella C. Glitza Oliva
Summary: Leptomeningeal disease (LMD) is a major challenge in the clinical management of metastatic melanoma patients. Recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients, and new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Review
Oncology
Larissa Anastacio DaCosta Carvalho, Flavia C. Aguiar, Keiran S. M. Smalley, Patricia A. Possik
Summary: Acral melanoma is a rare subtype of melanoma that is not linked to sun exposure. Recent studies have begun to explore the genetics and immune features of acral melanoma, which can provide guidance for therapeutic management.
