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
Biochemistry & Molecular Biology
Elena Lastraioli, Federico Alessandro Ruffinatti, Giacomo Bagni, Luca Visentin, Francesco di Costanzo, Luca Munaron, Annarosa Arcangeli
Summary: In melanoma, immune response and proteasome are associated with tumor development, while genes related to cytosolic ribosomes show a downregulated trend, and transcripts coding for mitoribosome proteins show the opposite trend.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Rossella Loria, Valentina Laquintana, Stefano Scalera, Rocco Fraioli, Valentina Caprara, Italia Falcone, Chiara Bazzichetto, Marta Di Martile, Laura Rosano, Donatella Del Bufalo, Gianluca Bossi, Isabella Sperduti, Irene Terrenato, Paolo Visca, Silvia Soddu, Michele Milella, Gennaro Ciliberto, Rita Falcioni, Virginia Ferraresi, Giulia Bon
Summary: This study reveals that high expression of SEMA6A is associated with poor prognosis in BRAF-mutant melanoma and plays a critical role in promoting tumor aggressiveness and resistance to targeted therapies. SEMA6A may serve as a potential predictor for the efficacy of dual BRAF/MEK inhibition.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Mehrdad Zarei, Omid Hajihassani, Jonathan J. Hue, Hallie J. Graor, Alexander W. Loftus, Moeez Rathore, Ali Vaziri-Gohar, John M. Asara, Jordan M. Winter, Luke D. Rothermel
Summary: This study explores the role of wtIDH1 in melanoma and finds that melanoma patients express higher levels of wtIDH1 and this is associated with poorer survival. Inhibiting wtIDH1 expression can inhibit cell proliferation and migration under nutrient limited conditions. Additionally, wtIDH1 inhibition synergizes with conventional anti-melanoma chemotherapy.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Parmanand Malvi, Dhana Sekhar Reddy, Raj Kumar, Suresh Chava, Sneha Burela, Keshab Parajuli, Xuchen Zhang, Narendra Wajapeyee
Summary: Melanoma, the leading cause of skin cancer-related deaths, is difficult to treat with current therapies due to resistance. However, the LIMK2 -> G3BP1 -> ESM1 pathway has been identified as a potential target for melanoma therapy, as inhibition of LIMK2 results in impaired tumor growth and metastasis. This pathway plays a crucial role in actin filament dynamics and has been found to be overexpressed in melanoma. Therefore, targeting LIMK2 could provide a promising strategy for improved melanoma treatment.
Article
Oncology
Zeynep Eroglu, Y. Ann Chen, Inna Smalley, Jiannong Li, Joseph K. Markowitz, Andrew S. Brohl, Leticia Tetteh, Hayley Taylor, Vernon K. Sondak, Nikhil I. Khushalani, Keiran S. M. Smalley
Summary: In this study, the efficacy and safety of vemurafenib and cobimetinib in combination with different doses of the HSP90 inhibitor XL888 for the treatment of advanced melanoma were explored. The study found that this combination therapy showed activity in some patients, but also had significant toxicity.
Review
Medicine, General & Internal
Alessandro Nepote, Gianluca Avallone, Simone Ribero, Francesco Cavallo, Gabriele Roccuzzo, Luca Mastorino, Claudio Conforti, Luca Paruzzo, Stefano Poletto, Fabrizio Carnevale Schianca, Pietro Quaglino, Massimo Aglietta
Summary: About 50% of melanomas have a BRAF mutation, with 10% of these having a V600K mutation. No specific studies have been conducted to establish a clinical and therapeutic gold standard for V600K melanoma patients. However, recent findings suggest that V600K melanoma is less dependent on the ERK/MAPK pathway and can be effectively treated with BRAF and MEK inhibitors or anti-checkpoint blockades. Nonetheless, V600K melanoma remains a medical need and is associated with poor prognosis.
JOURNAL OF CLINICAL MEDICINE
(2022)
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)
Article
Biochemistry & Molecular Biology
Ernesto Rossi, Giovanni Schinzari, Francesco Cellini, Mario Balducci, Mariangela Pasqualoni, Brigida Anna Maiorano, Bruno Fionda, Silvia Longo, Francesco Deodato, Alessandro Di Stefani, Ketty Peris, Maria Antonietta Gambacorta, Giampaolo Tortora
Summary: BRAF and MEK inhibitors have changed the clinical management of metastatic melanoma, but their combination with radiotherapy needs careful monitoring for potential toxicity. This study reports the successful use of fractionated radiotherapy in metastatic melanoma patients receiving BRAF and MEK inhibitors, without significant adverse events. These results suggest that interruption of targeted therapy during radiotherapy for oligoprogressive disease can be avoided.
Article
Oncology
H. Gogas, B. Dreno, J. Larkin, L. Demidov, D. Stroyakovskiy, Z. Eroglu, P. Francesco Ferrucci, J. Pigozzo, P. Rutkowski, J. Mackiewicz, I Rooney, A. Voulgari, S. Troutman, B. Pitcher, Y. Guo, Y. Yan, M. Castro, S. Mulla, K. Flaherty, A. Arance
Summary: The combination therapy of MEK inhibitors and immune checkpoint inhibitors did not show improved progression-free survival compared to monotherapy with pembrolizumab in patients with previously untreated BRAF(V600) wild-type advanced melanoma.
ANNALS OF ONCOLOGY
(2021)
Article
Oncology
Orsolya Pipek, Laura Vizkeleti, Viktoria Doma, Donat Alpar, Csaba Bödör, Sarolta Karpati, Jozsef Timar
Summary: Malignant melanoma of the skin, primarily on UV-exposed skin, is commonly associated with mutant BRAF, RAS, and KIT oncogenes. The genetic makeup of triple-wild-type melanoma (BRAF, NRAS, and NF1) has been studied before, but with mixed rare and common histopathological subtypes. In this study, whole genome sequencing was used to characterize triple-wild-type melanoma, excluding rare histopathological subtypes. Unrecognized drivers were identified among passenger mutations in some cases.
Review
Pharmacology & Pharmacy
Simeng Zhang, Zichang Yang, Yu Cheng, Xiaoyu Guo, Chang Liu, Shuo Wang, Lingyun Zhang
Summary: This study reported a case of a 64-year-old female metastatic melanoma patient with a novel BRAF p.L485-P490 deletion mutation. The patient was initially treated with the PD1 antibody pembrolizumab but discontinued due to intolerable adverse effects. As the p.L485-P490 deletion mutation resembled a class II BRAF mutation, the patient underwent second-line treatment with dabrafenib and trametinib combination therapy. After two cycles, the patient achieved partial response confirmed by radiological examinations and obtained over 18 months of progression-free survival at the last follow-up.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Manchao Zhang, Scarlett Acklin, John Gillenwater, Wuying Du, Mousumi Patra, Hao Yu, Bo Xu, Jianhua Yu, Fen Xia
Summary: Our study demonstrates that SIRT2 promotes melanoma tumor growth by reducing the number and function of tumor-infiltrating NK cells. Pharmacological inhibition of SIRT2 increases NK cell infiltration and suppresses tumor growth. These findings suggest that SIRT2 has the potential to mediate immunotherapy response and resistance in melanoma.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Karam Khaddour, Lucas Maahs, Ana Maria Avila-Rodriguez, Yazan Maamar, Sami Samaan, George Ansstas
Summary: Melanoma has shown significant advancements in management through the introduction of molecular targeted therapy (BRAF and MEK inhibitors) and immunotherapy (Immune checkpoint inhibitors). The high rate of somatic mutations in melanomas contributes to the development of targeted treatments leading to improved outcomes. Currently, BRAF and MEK inhibitors are the main approved targeted therapy for BRAF(V600E/K) mutant melanomas, while ongoing research is focusing on novel individualized treatment approaches for non-BRAF mutations in melanomas.
Article
Oncology
Lukas Peiffer, Farnoush Farahpour, Ashwin Sriram, Ivelina Spassova, Daniel Hoffmann, Linda Kubat, Patrizia Stoitzner, Thilo Gambichler, Antje Sucker, Selma Ugurel, Dirk Schadendorf, Jurgen C. Becker
Summary: The study found that treatment with BRAF/MEK inhibitors in melanoma patients allows for an increased expansion of pre-existing melanoma-specific T cells by inducing T-bet and TCF7.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Christopher Korch, Erin M. Hall, Wilhelm G. Dirks, Margaret Ewing, Mark Faries, Marileila Varella-Garcia, Steven Robinson, Douglas Storts, Jacqueline A. Turner, Ying Wang, Edward C. Burnett, Lyn Healy, Douglas Kniss, Richard M. Neve, Raymond W. Nims, Yvonne A. Reid, William A. Robinson, Amanda Capes-Davis
INTERNATIONAL JOURNAL OF CANCER
(2018)
Article
Immunology
Richard P. Tobin, Kimberly R. Jordan, William A. Robinson, Dana Davis, Virginia F. Borges, Rene Gonzalez, Karl D. Lewis, Martin D. McCarter
INTERNATIONAL IMMUNOPHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Jacqueline A. Turner, Judson G. T. Bemis, Stacey M. Bagby, Anna Capasso, Betelehem W. Yacob, Tugs-Saikhan Chimed, Robert Van Gulick, Hannah Lee, Richard Tobin, John J. Tentler, Todd Pitts, Martin McCarter, William A. Robinson, Kasey L. Couts
Article
Oncology
Dinoop Ravindran Menon, Yuchun Luo, John J. Arcaroli, Sucai Liu, Lekha Nair KrishnanKutty, Douglas G. Osborne, Yang Li, Jenny Mae Samson, Stacey Bagby, Aik-Choon Tan, William A. Robinson, Wells A. Messersmith, Mayumi Fujita
Article
Oncology
Iwei Yeh, Eric Jorgenson, Ling Shen, Mengshu Xu, Jeffrey P. North, A. Hunter Shain, David Reuss, Hong Wu, William A. Robinson, Adam Olshen, Andreas von Deimling, Pui-Yan Kwok, Boris C. Bastian, Maryam M. Asgari
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2019)
Article
Oncology
Anna G. Mackin, Paula E. Pecen, Amanda L. Dinsmore, Jennifer L. Patnaik, Rene Gonzalez, William A. Robinson, Alan G. Palestine
Article
Biochemistry & Molecular Biology
Douglas G. Osborne, Joanne Domenico, Yuchun Luo, Anna L. Reid, Carol Amato, Zili Zhai, Dexiang Gao, Melanie Ziman, Charles A. Dinarello, William A. Robinson, Mayumi Fujita
MOLECULAR CARCINOGENESIS
(2019)
Article
Oncology
Alison L. Halpern, Robert J. Torphy, Martin D. McCarter, Cosimo G. Sciotto, L. Michael Glode, William A. Robinson
Review
Cell Biology
Tal Burstyn-Cohen, Avi Maimon
CELL COMMUNICATION AND SIGNALING
(2019)
Article
Oncology
Chloe Friedman, Madison Lyon, Robert J. Torphy, Daniel Thieu, Patrick Hosokawa, Rene Gonzalez, Karl D. Lewis, Theresa M. Medina, Matthew J. Rioth, William A. Robinson, Nicole Kounalakis, Martin D. McCarter, Ana L. Gleisner
JOURNAL OF SURGICAL ONCOLOGY
(2019)
Article
Oncology
Richard P. Tobin, Kimberly R. Jordan, Puja Kapoor, Eric Spongberg, Dana Davis, Victoria M. Vorwald, Kasey L. Couts, Dexiang Gao, Derek E. Smith, Jessica S. W. Borgers, Steven Robinson, Carol Amato, Rene Gonzalez, Karl D. Lewis, William A. Robinson, Virginia F. Borges, Martin D. McCarter
FRONTIERS IN ONCOLOGY
(2019)
Article
Dermatology
Nabanita Mukherjee, Chiara R. Dart, Carol M. Amato, Adam Honig-Frand, James R. Lambert, Karoline A. Lambert, William A. Robinson, Richard P. Tobin, Martin D. McCarter, Kasey L. Couts, Mayumi Fujita, David A. Norris, Yiqun G. Shellman
Summary: Uveal melanoma (UM) has a distinct expression profile of BCL2 family members compared to other cancer types, making them susceptible to BCL2 homologous 3 mimetics. UM is more sensitive to MCL1 inhibitor (MCL1i), and overexpression of BFL1 or knockdown of PUMA can increase UM resistance to MCL1i. Combination therapy of MCL1i with BCL2 inhibitor synergistically inhibits UM initiating cells expansion.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Immunology
Tal Burstyn-Cohen, Roberta Fresia
Summary: TYRO3, AXL, and MERTK are members of the TAM family of receptor tyrosine kinases, which are activated by their ligands GAS6 and PROS1. TAMs play vital roles in adult homeostasis in various systems. Phagocytosis is a central function employed by TAMs to maintain tissue health.
IMMUNOLOGICAL REVIEWS
(2023)