Article
Oncology
Joanna Lee, Tasnia Ahmed, Andrea Maurichi, Lorenzo Di Guardo, Anna M. Stagno, Lydia Warburton, Amelia. M. Taylor, Elisabeth Livingstone, Saba Rehman, Adnan Khattak, Katharina C. Kahler, Vito Vanella, Victoria Atkinson, Michael Millward, Dirk Schadendorf, Douglas B. Johnson, Paolo A. Ascierto, Axel Hauschild, Serigne N. Lo, Georgina V. Long, Alexander M. Menzies, Matteo S. Carlino
Summary: For patients with advanced melanoma, there is a risk of recurrence after discontinuation of targeted therapy, but retreatment with targeted therapy shows a high response rate.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Sara J. Hamis, Yury Kapelyukh, Aileen McLaren, Colin J. Henderson, C. Roland Wolf, Mark A. J. Chaplain
Summary: The study developed a mechanistic mathematical model to describe the synergistic action of dabrafenib and trametinib on ERK activity in BRAFV600E-mutant melanoma cells, elucidating the molecular mechanism underlying vertical inhibition of the BRAF-MEK-ERK cascade.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Nikolina Pitesa, Matea Kurtovic, Nenad Bartonicek, Danai S. Gkotsi, Josipa Conkas, Tina Petric, Vesna Musani, Petar Ozretic, Natalia A. Riobo-Del Galdo, Maja Sabol
Summary: Melanoma is a deadly form of skin cancer and understanding its resistance to treatment is crucial. This study investigates the role of non-canonical signaling interactions in melanoma chemoresistance, specifically focusing on the HH-GLI and RAS/RAF/ERK pathways. Through establishing melanoma cell lines resistant to the GLI inhibitor GANT-61, the study provides insights into potential mechanisms involved in resistance and highlights the importance of non-canonical signaling interactions.
Article
Multidisciplinary Sciences
Pattra Chun-on, Angela M. Hinchie, Holly C. Beale, Agustin A. Gil Silva, Elizabeth Rush, Cindy Sander, Carla J. Connelly, Brittani K. N. Seynnaeve, John M. Kirkwood, Olena M. Vaske, Carol W. Greider, Jonathan K. Alder
Summary: TERT promoter mutations alone are insufficient to maintain telomeres in melanoma, but together with TPP1 promoter variants, they synergistically enhance telomere maintenance and immortalization in melanoma.
Article
Oncology
Rahim Ullah, Qing Yin, Aidan H. Snell, Lixin Wan
Summary: The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway that plays a critical role in cell proliferation and survival. Genetic alterations in this pathway are highly prevalent in human cancers and can lead to uncontrolled cell growth and tumor formation. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further enhances its proliferative potential in human cancers.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Clint A. Stalnecker, Kajal R. Grover, A. Cole Edwards, Michael F. Coleman, Runying Yang, Jonathan M. DeLiberty, Bjorn Papke, Craig M. Goodwin, Mariaelena Pierobon, Emanuel F. Petricoin, Prson Gautam, Krister Wennerberg, Adrienne D. Cox, Channing J. Der, Stephen D. Hursting, Kirsten L. Bryant
Summary: Pancreatic ductal adenocarcinoma (PDAC) is aggressive and requires improved therapies. Recent research has shown that autophagy, a macrometabolic process, is upregulated in PDAC and essential for its growth. However, the clinical efficacy of autophagy inhibition as a monotherapy is limited. Targeting both insulin-like growth factor 1 receptor (IGF1R) and pathways that oppose autophagy, such as the ERK-MAPK axis, can enhance the effectiveness of autophagy inhibitors in PDAC.
Article
Oncology
Da Wang, Fei Xiong, Guanhua Wu, Wenzheng Liu, Bing Wang, Yongjun Chen
Summary: The study found that in cholangiocarcinoma, miR-155-5p targets the 3' UTR of SOX1, activating the RAF/MEK/ERK pathway and promoting cancer progression.
CANCER CELL INTERNATIONAL
(2021)
Article
Oncology
Saketh S. Dinavahi, Yu-Chi Chen, Kishore Punnath, Arthur Berg, Meenhard Herlyn, Momeneh Foroutan, Nicholas D. Huntington, Gavin P. Robertson
Summary: The targeting of the AKT/WEE1 pathways to induce p53 activation is a novel and effective approach to inhibit tumor development. This study shows that this approach can enhance tumor immunogenicity, induce immunogenic cell death, and recruit immune cells in the tumor microenvironment, resulting in tumor regression.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Georgii Dolgalev, Ekaterina Poverennaya
Summary: In the past 8 years, studies have revealed the widespread occurrence of isoform switching in human cancers with hundreds to thousands of events per cancer type. However, the relationship between changes in transcript usage and transcript expression has not been adequately explored. In this article, the authors use a state-of-the-art tool, SatuRn, to detect isoform switching events in 12 cancer types and analyze the relationship between transcript usage and expression on a global scale. The results suggest that this quantitative information can effectively prioritize isoform switching events for further analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Yun Zhang, Katherine M. Weh, Connor L. Howard, Jean-Jack Riethoven, Jennifer L. Clarke, Kiran H. Lagisetty, Jules Lin, Rishindra M. Reddy, Andrew C. Chang, David G. Beer, Laura A. Kresty
Summary: This study used next-generation sequencing to analyze isoform switching events in esophageal adenocarcinoma and found their association with tissue histopathology and TP53 mutation status. It also identified certain isoforms that were significantly linked to patient survival.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Oncology
Kevin Yao, Emily Zhou, Chao Cheng
Summary: In this study, a B-Raf signature score was defined using RNA-seq data, which could predict B-Raf mutation status and other aberrations. Patients dichotomized by the median B-Raf score showed more significant stratification compared to other metrics. High B-Raf score also predicted higher sensitivity to B-Raf inhibitors and drugs targeting other relevant oncogenic pathways.
Article
Cell Biology
Jie Zhou, Daoyuan Tu, Rui Peng, Yuhong Tang, Qiangwei Deng, Bingbing Su, Shunyi Wang, Hao Tang, Shengjie Jin, Guoqing Jiang, Qian Wang, Xin Jin, Chi Zhang, Jun Cao, Dousheng Bai
Summary: Through tissue microarray and immunohistochemistry staining, it was found that RNF173 expression is significantly lower in hepatocellular carcinoma (HCC) patients and is closely related to their survival and recurrence rates. Experimental results showed that RNF173 inhibits the invasion and metastasis of HCC through degradation of GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. Therefore, RNF173 may serve as a novel prognostic molecular and potential therapeutic target for HCC.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Behavioral Sciences
Joy D. Iroegbu, Olayemi K. Ijomone, Omowumi M. Femi-Akinlosotu, Omamuyovwi M. Ijomone
Summary: The ERK/MAPK signaling pathway plays a crucial role in neurodevelopment, particularly in the development of neural progenitor cells and the proper formation of the nervous system. It is associated with various neurodevelopmental disorders, highlighting its significance in understanding the pathology of these disorders and identifying potential novel therapeutic targets.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Review
Cell Biology
Reiko Sugiura, Ryosuke Satoh, Teruaki Takasaki
Summary: The RAF/MEK/ERK signaling pathway regulates various cellular processes and its activation is linked to cell proliferation and cancer. Further research on the mechanisms of ERK activation is essential for developing effective cancer treatments.
Article
Oncology
Prashanthi Dharanipragada, Xiao Zhang, Sixue Liu, Shirley H. Lomeli, Aayoung Hong, Yan Wang, Zhentao Yang, Kara Z. Lo, Agustin Vega-Crespo, Antoni Ribas, Stergios J. Moschos, Gatien Moriceau, Roger S. Lo
Summary: Blocking cancer genomic instability prevents tumor diversification and therapy escape. Acquired resistant genomes of metastatic cutaneous melanoma amplify nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR) genes via complex genomic rearrangements (CGR) and extrachromosomal DNAs (ecDNA). NHEJ targeting by a DNA-PKCS inhibitor prevents acquired MAPKi resistance by reducing the size of ecDNAs and CGRs.
Article
Dermatology
M. Roelens, A. de Masson, C. Ram-Wolff, G. Maki, J-M. Cayuela, A. Marie-Cardine, A. Bensussan, A. Toubert, M. Bagot, H. Moins-Teisserenc
BRITISH JOURNAL OF DERMATOLOGY
(2020)
Article
Rheumatology
Charles Cassius, Mylene Branchtein, Maxime Battistella, Reyhan Amode, Clemence Lepelletier, Marie Jachiet, Adele de Masson, Laure Frumholtz, Francois Chasset, Zahir Amoura, Alexis Mathian, Assia Samri, Jean-Benoit Monfort, Claude Bachmeyer, Djaouida Bengoufa, Florence Cordoliani, Martine Bagot, Armand Bensussan, Jean-David Bouaziz, Helene Le Buanec
Review
Oncology
Nicolas Dumaz, Celeste Lebbe
Summary: Recent studies on the regulation of the MAPK pathway have focused on the dominant role of dimers in RAF, MEK, and ERK, leading to the development of allosteric inhibitors targeting these dimers. The primary goal in the development of next-generation RAF, MEK, and ERK inhibitors is to produce molecules with less off-target effects and sustained pathway inhibition.
CURRENT OPINION IN ONCOLOGY
(2021)
Review
Oncology
Pauline Tetu, Laetitia Vercellino, Coralie Reger de Moura, Barouyr Baroudjian, Nicolas Dumaz, Samia Mourah, Celeste Lebbe
Summary: Although targeted therapy provides a high response rate and rapid disease control in advanced melanoma, acquired resistance mechanisms often lead to disease progression. Recent studies have explored intermittent dosing of BRAF and MEK inhibitors as a potential way to prevent lethal drug resistance, but results have been inconclusive with some showing no advantage over continuous dosing. Additional clinical data is needed to determine the optimal therapeutic approach.
CURRENT OPINION IN ONCOLOGY
(2021)
Article
Dermatology
Justine Habault, Nicolas Thonnart, Ewa Pasquereau-Kotula, Martine Bagot, Armand Bensussan, Bruno O. Villoutreix, Anne Marie-Cardine, Jean-Luc Poyet
Summary: The study demonstrates that the peptide RT39 shows potential therapeutic effects in the specific elimination of the malignant T-cell clone in Sezary syndrome, by binding to PAK1 and inducing selective depletion of the cells through membranolysis. Additionally, RT39 displays good safety profile.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Hematology
Gabrielle Sonigo, Alizee Bozonnat, Maelle Dumont, Nicolas Thonnart, Caroline Ram-Wolff, Adele de Masson, Martine Bagot, Armand Bensussan, Anne Marie-Cardine
Article
Oncology
Andrey A. Yurchenko, Oltin T. Pop, Meriem Ighilahriz, Ismael Padioleau, Fatemeh Rajabi, Hayley J. Sharpe, Nicolas Poulalhon, Brigitte Dreno, Amir Khammari, Marc Delord, Antonio Alberti, Nadem Soufir, Maxime Battistella, Samia Mourah, Fanny Bouquet, Ariel Savina, Andrej Besse, Max Mendez-Lopez, Florent Grange, Sandrine Monestier, Laurent Mortier, Nicolas Meyer, Caroline Dutriaux, Caroline Robert, Philippe Saiag, Florian Herms, Jerome Lambert, Frederic J. de Sauvage, Nicolas Dumaz, Lukas Flatz, Nicole Basset-Seguin, Sergey Nikolaev
Summary: This study found that intrinsic resistance (IR) to vismodegib in locally advanced basal cell carcinoma (laBCC) is rare. IR-BCC patients often have resistance mutations in the Hh pathway, but also exhibit hyperactivation of the HIPPO-YAP and WNT pathways.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ahlem Jebali, Maxime Battistella, Celeste Lebbe, Nicolas Dumaz
Summary: The network involving PI3K, AKT, and mTOR is important in melanoma oncogenesis, with RICTOR overexpression associated with poor prognosis. RICTOR enhances melanoma-initiating cells with stemness properties and contributes to resistance to BRAF inhibitors. An interaction between RICTOR and STAT3 in resistant cells, as well as a connection between RAS and RICTOR in resistant melanoma, were identified, suggesting RICTOR as a valuable therapeutic target in melanoma.
Article
Oncology
Marie-Lea Gauci, Jerome Giustiniani, Clemence Lepelletier, Christian Garbar, Nicolas Thonnart, Nicolas Dumaz, Arnaud Foussat, Celeste Lebbe, Armand Bensussan, Anne Marie-Cardine
Summary: Research has found that CD160 is highly expressed in the tumor tissues of melanoma patients. Melanoma cells express CD160-GPI isoform and release soluble form (sCD160), which inhibits the cytotoxic activity of NK cells. In addition, sCD160 is found in the serum of melanoma patients and is associated with increased tumor dissemination.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
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.
Letter
Dermatology
Andreea Calugareanu, Adele de Masson, Maxime Battistella, Laurence Michel, Caroline Ramwolff, Jean-David Bouaziz, Sandy Peltier, Armand Bensussan, Martin Bagot, Gabor Dobos
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Julie Delyon, Anais Vallet, Melanie Bernard-Cacciarella, Isabelle Kuzniak, Coralie Reger de Moura, Baptiste Louveau, Fanelie Jouenne, Samia Mourah, Celeste Lebbe, Nicolas Dumaz
Summary: TERT promoter mutations are frequently found in melanoma and are associated with a poorer prognosis. Our data suggest that TERT mRNA level is a reliable marker for prognosis and is associated with resistance to targeted therapy in melanoma. We showed that TERT overexpression drives resistance to BRAF and MEK inhibitors, and inhibition of TERT can be a therapeutic option for melanoma with acquired resistance to BRAF inhibition.
Article
Cell Biology
Antonio Arulanandam, Liang Lin, Hao-Ming Chang, Martine Cerutti, Sylvie Choblet, Peng Gao, Armin Rath, Armand Bensussan, Jean Kadouche, Daniel Teper, Ofer Mandelboim, Wei Li
Summary: GPC3 is highly expressed in multiple solid tumors and is barely expressed in adult normal tissues except the placenta. NKp46 activation receptor is expressed in all-natural killer cells, including tumor-infiltrating NK cells. CYT-303 is a multifunctional antibody that targets both GPC3 and NKp46 to mediate NK cell-redirected killing of HCC tumors.
Meeting Abstract
Pharmacology & Pharmacy
F. Jouenne, B. Louveau, P. Tetu, A. Sadoux, A. Gruber, E. Lopes, J. Delyon, K. Serror, O. Marco, L. Da Meda, A. Ndiaye, A. Lermine, N. Dumaz, M. Battistella, B. Baroudjian, C. Lebbe, S. Mourah
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
B. Louveau, F. Jouenne, C. Reger De Moura, A. Sadoux, B. Baroudjian, J. Delyon, F. Herms, A. De Masson, L. Da Meda, M. Battistella, N. Dumaz, C. Lebbe, S. Mourah
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2021)