Article
Oncology
Bob Meeusen, Emanuela Elsa Cortesi, Judit Domenech Omella, Anna Sablina, Juan-Jose Ventura, Veerle Janssens
Summary: This study found that the loss of PP2A activator PTPA in KRAS-mutant lung adenocarcinomas is associated with poorer overall survival, increased cell growth, and accelerated tumor formation. Additionally, the depletion of PPP2R4 induced resistance against MEK inhibitor but sensitized cells to mTOR inhibitor, highlighting its clinical relevance in NSCLC etiology and kinase inhibitor response.
Article
Cell Biology
Simon Lizarazo, Yeeun Yook, Nien-Pei Tsai
Summary: Alzheimer's disease is a common form of dementia, characterized by the accumulation of amyloid beta peptide. This study reveals that Fmr1 is involved in A beta-induced translational suppression, leading to hyposynchrony of neuronal firing activity and loss of excitatory synapses. The mechanism involves the repression of phosphatases by Fmr1, resulting in translational suppression.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Ni An, Zhenjie Li, Xiaodi Yan, Hainan Zhao, Yajie Yang, Ruling Liu, Yanyong Yang, Fu Gao, Bailong Li, Hu Liu, Hongbin Yuan
Summary: This study found that the inhibition of Rac1 plays an important role in protecting against radiation-induced lung injury and suppressing lung tumor growth. It reduces apoptosis in normal lung epithelial cells, alleviating RILI, and also inhibits lung tumor growth and increases the sensitivity of tumor cells to radiation.
CELL DEATH DISCOVERY
(2022)
Article
Pharmacology & Pharmacy
Nongyao Nonpanya, Kittipong Sanookpan, Nicharat Sriratanasak, Chanida Vinayanuwattikun, Duangdao Wichadakul, Boonchoo Sritularak, Pithi Chanvorachote
Summary: Artocarpin targets FAK to suppress EMT and migratory behaviors of lung cancer cells, without affecting normal lung cells.
Article
Multidisciplinary Sciences
Sutthaorn Pothongsrisit, Kuntarat Arunrungvichian, Yoshihiro Hayakawa, Boonchoo Sritularak, Supachoke Mangmool, Varisa Pongrakhananon
Summary: Erianthridin (ETD) inhibits cell migration and invasion by disrupting actin stress fibers and lamellipodia formation, downregulating MMP-2 and MMP-9 expression. It also attenuates Akt/mTOR/p70(S6K) signaling pathway, leading to suppression of lung cancer metastasis. These findings suggest ETD as a promising antimetastatic agent against non-small-cell lung cancer.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Mingyu Chen, Hanyue Li, Xiaolin Xu, Xunxia Bao, Lei Xue, Xinghao Ai, Jian Xu, Ming Xu, Yong Shi, Timing Zhen, Jie Li, Yi Yang, Yang Ji, Zhiliang Fu, Kaichen Xing, Tao Qing, Qiubo Wang, Ping Zhong, Sibo Zhu
Summary: This study investigated the biomarkers, pathways, and potential therapeutics for lung adenocarcinoma brain metastasis. The researchers identified metastasis-related biomarkers and validated the cancer metastatic hallmark. They also demonstrated the critical role of RAC1 in LUAD metastasis and its potential as a therapeutic target. Functional experiments and animal models further supported the promotion of brain metastasis by RAC1. Overall, this study provides new insights into the understanding and treatment of LUAD brain metastasis.
CELL DEATH & DISEASE
(2023)
Article
Biology
Yu-Hsuan Chen, Jinn-Yuan Hsu, Ching-Tung Chu, Yao-Wen Chang, Jia-Rong Fan, Muh-Hwa Yang, Hong-Chen Chen
Summary: In this study, the researchers used HNSCC cells as a model to investigate the mechanism of cell migration upon loss of cell-cell adhesion. They found that reactive oxygen species (ROS) generation and vimentin expression were induced by the loss of adhesion, and both were necessary for cell migration. The study also demonstrated that Tiam1-mediated Rac1 activation was responsible for ROS generation, and the ROS-Src-STAT3 signaling pathway played an important role in cell migration.
LIFE SCIENCE ALLIANCE
(2022)
Article
Immunology
Gerco den Hartog, Lindsay D. Butcher, Amber L. Ablack, Laura A. Pace, Jailal N. G. Ablack, Richard Xiong, Soumita Das, Thaddeus S. Stappenbeck, Lars Eckmann, Peter B. Ernst, Sheila E. Crowe
Summary: APE1 negatively regulates Rac1 to inhibit invasive bacteria from entering human intestinal epithelial cells, protecting the barrier function of epithelial cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Alessia Floerchinger, Kendelle J. Murphy, Sharissa L. Latham, Sean C. Warren, Andrew T. McCulloch, Young-Kyung Lee, Janett Stoehr, Pauline Melenec, Cris S. Guaman, Xanthe L. Metcalf, Victoria Lee, Anaiis Zaratzian, Andrew Da Silva, Michael Tayao, Sonia Rolo, Monica Phimmachanh, Ghazal Sultani, Laura McDonald, Susan M. Mason, Nicola Ferrari, Lisa M. Ooms, Anna-Karin E. Johnsson, Heather J. Spence, Michael F. Olson, Laura M. Machesky, Owen J. Sansom, Jennifer P. Morton, Christina A. Mitchell, Michael S. Samuel, David R. Croucher, Heidi C. E. Welch, Karen Blyth, C. Elizabeth Caldon, David Herrmann, Kurt Anderson, Paul Timpson, Max Nobis
Summary: Assessing drug response within live native tissue provides increased fidelity in optimizing efficacy and minimizing off-target effects. Using single-cell intravital imaging, this study demonstrates that Rac1 inhibition can reduce tumor progression and metastases to improve overall survival in an autochthonous setting. The study also reveals enhanced Rac1 activity of cells near live tumor vasculature, and how Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress for better anti-metastatic response during transit to secondary sites.
Article
Oncology
Subbulakshmi Karthikeyan, Patrick J. Casey, Mei Wang
Summary: This study identifies the RAB4A-RAC1 signaling axis as a key regulatory mechanism for EMT and cancer progression, suggesting a potential therapeutic approach to controlling these processes.
BREAST CANCER RESEARCH
(2022)
Article
Immunology
Karmele Valencia, Mirari Echepare, Alvaro Teijeira, Andrea Pasquier, Cristina Bertolo, Cristina Sainz, Ibon Tamayo, Benat Picabea, Graziella Bosco, Roman Thomas, Jackeline Agorreta, Jose Maria Lopez-Picazo, Joan Frigola, Ramon Amat, Alfonso Calvo, Enriqueta Felip, Ignacio Melero, Luis M. Montuenga
Summary: Valencia et al. have identified DSTYK as a novel therapeutic target in lung cancer. Inhibition of DSTYK sensitizes lung cancer cells to T cell-mediated killing and impairs mitochondrial fitness and cytoprotective autophagy. DSTYK copy number gain predicts lack of response to immunotherapy in lung cancer patients.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yu Wang, Ran Zuo, Gengwei Huo, Zhiqiang Han, Yuchao He, Yi Luo, Liwei Chen, Guangtao Li, Jinfang Cui, Fuyi Zhu, Ping Yue, Dongqi Yuan, Yi Sun, Zhaoyue Li, Peng Chen, Hua Guo
Summary: Numerous studies have demonstrated the crucial involvement of actin cytoskeleton in cancer initiation and progression. As an actin-binding protein, Twinfilin1 (TWF1) is known to regulate cytoskeleton-related functions. However, the expression and function of TWF1 in human tumors, particularly in lung adenocarcinoma (LUAD), remain poorly understood.
Article
Cell Biology
Caroline Eiden, Hendrik Ungefroren
Summary: The study found that the protein expression of RAC1B and RAC1 in breast cancer cells is associated with phenotypes, where high RAC1B and low RAC1 predict an epithelial phenotype, while low RAC1B and high RAC1 are distinguishing features of the mesenchymal state. This suggests that the combined quantitative assessment of RAC1B and RAC1 in tumor biopsies of breast cancer patients may be a novel diagnostic tool for probing molecular subtype and predicting the malignant potential of breast tumors.
Article
Oncology
Mario Scarpa, Prerna Singh, Christopher M. Bailey, Jonelle K. Lee, Shivani Kapoor, Rena G. Lapidus, Sandrine Niyongere, Jaya Sangodkar, Yin Wang, Danilo Perrotti, Goutham Narla, Maria R. Baer
Summary: PADs can enhance efficacy of FLT3 inhibitors in FLT3-ITD-expressing cells through increased growth suppression and apoptosis induction, by inducing AKT inhibition-dependent GSK-3b-mediated c-Myc and Pim-1 protein degradation.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Microbiology
Edwin Lasonder, Kunal More, Shailja Singh, Malak Haidar, Daniela Bertinetti, Eileen J. Kennedy, Friedrich W. Herberg, Anthony A. Holder, Gordon Langsley, Chetan E. Chitnis
Summary: The review emphasizes the significance of signaling pathways in regulating key processes during Plasmodium falciparum infection, particularly highlighting the roles of cAMP and Ca2+ and the involvement of PKA in red blood cell invasion. Additionally, it suggests utilizing these pathways as potential therapeutic targets for treating malaria and other diseases caused by apicomplexan parasites.
FRONTIERS IN MICROBIOLOGY
(2021)
Meeting Abstract
Oncology
J. L. Lacaze, C. Chira, G. Glemarec, R. Aziza, E. De Maio, F. Izar, E. Jouve, C. Massabeau, A. Pradines, G. Selmes, M. Ung, S. Zerdoud, F. Dalenc
ANNALS OF ONCOLOGY
(2020)
Article
Pathology
Cathy Quelen, David Grand, Emeline Sarot, Laurence Brugieres, David Sibon, Anne Pradines, Camille Laurent, Pierre Brousset, Laurence Lamant
Summary: In ALK-positive anaplastic large-cell lymphomas, real-time quantitative PCR can identify high-risk patients, but the current technique designed for patients with the most common NPM1-ALK translocation has reproducibility issues among different laboratories.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2021)
Article
Oncology
David Gandara, Martin Reck, Denis Moro-Sibilot, Julien Mazieres, Shirish Gadgeel, Stefanie Morris, Andres Cardona, Diana Mendus, Marcus Ballinger, Achim Rittmeyer, Solange Peters
Summary: The study aimed to develop criteria for fast progression (FP) by analyzing data from the randomized phase III OAK study, showing that FP rates were similar with atezolizumab and docetaxel and suggesting that FP may not be unique to checkpoint inhibitors, although the underlying mechanisms may differ from those of chemotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Bryan Ulrich, Anne Pradines, Julien Mazieres, Nicolas Guibert
Summary: Circulating tumor DNA is a novel biomarker that shows potential in predicting cancer relapse and guiding adjuvant therapies. In patients with localized disease, ctDNA kinetics is considered a highly sensitive and specific marker for relapse. Further research is needed to explore the full potential of ctDNA as a tool for personalized treatment in non-small-cell lung cancer.
Article
Oncology
Jean-Louis Lacaze, Richard Aziza, Ciprian Chira, Eleonora De Maio, Francoise Izar, Eva Jouve, Carole Massabeau, Anne Pradines, Gabrielle Selmes, Mony Ung, Slimane Zerdoud, Florence Dalenc
Summary: Oligometastatic breast cancer (OMBC) lacks a standardized treatment strategy, with limited information provided by existing literature. Research on OMBC biological characteristics suggests a focus on circulating tumor cell counts, as well as development of studies on microRNAs, circulating tumor DNA, and genomic alterations.
Article
Oncology
Xiuning Le, Hiroshi Sakai, Enriqueta Felip, Remi Veillon, Marina Chiara Garassino, Jo Raskin, Alexis B. Cortot, Santiago Viteri, Julien Mazieres, Egbert F. Smit, Michael Thomas, Wade T. Iams, Byoung Chul Cho, Hye Ryun Kim, James Chih-Hsin Yang, Yuh-Min Chen, Jyoti D. Patel, Christine M. Bestvina, Keunchil Park, Frank Griesinger, Melissa Johnson, Maya Gottfried, Christian Britschgi, John Heymach, Elif Sikoglu, Karin Berghoff, Karl-Maria Schumacher, Rolf Bruns, Gordon Otto, Paul K. Paik
Summary: Tepotinib demonstrated durable clinical activity in patients with METex14 skipping non-small cell lung cancer and consistent efficacy and manageable safety profile across different subgroups.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Egbert F. Smit, Christophe Dooms, Jo Raskin, Ernest Nadal, Lye M. Tho, Xiuning Le, Julien Mazieres, How S. Hin, Masahire Morise, Viola W. Zhu, Daniel Tan, Kristina H. Holmberg, Barbara Ellers-Lenz, Svenja Adrian, Sabine Brutlach, Karl M. Schumacher, Niki Karachaliou, Yi-Long Wu
Summary: Combining osimertinib with MET inhibitor like tepotinib could potentially overcome resistance driven by MET amplification in NSCLC patients, and the ongoing study INSIGHT 2 aims to evaluate the efficacy and safety of this combination therapy for patients with acquired resistance to osimertinib due to MET amplification.
Article
Oncology
Julien Mazieres, Claire Lafitte, Charles Ricordel, Laurent Greillier, Elodie Negre, Gerard Zalcman, Charlotte Domblides, Jeannick Madelaine, Jaafar Bennouna, Celine Mascaux, Denis Moro-Sibilot, Francois Pinquie, Alexis B. Cortot, Josiane Otto, Jacques Cadranel, Alexandra Langlais, Franck Morin, Virginie Westeel, Benjamin Besse
Summary: This study evaluated the efficacy of a triple therapy with HER2-targeted antibodies and docetaxel in HER2-mutated NSCLC patients, demonstrating feasibility and effectiveness of this approach, highlighting the potential benefit of HER2 antibody-based strategy in this subset of patients.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nino Iakobachvili, Stephen Adonai Leon-Icaza, Kevin Knoops, Norman Sachs, Serge Mazeres, Roxane Simeone, Antonio Peixoto, Celia Bernard, Marlene Murris-Espin, Julien Mazieres, Kaymeuang Cam, Christian Chalut, Christophe Guilhot, Carmen Lopez-Iglesias, Raimond B. G. Ravelli, Olivier Neyrolles, Etienne Meunier, Geanncarlo Lugo-Villarino, Hans Clevers, Celine Cougoule, Peter J. Peters
Summary: The study found that Mycobacterium tuberculosis and Mycobacterium abscessus mainly exist as extracellular bacteria in human airway organoids, infecting epithelial cells with low efficiency. The organoids respond to infection by modulating cytokine, antimicrobial peptide, and mucin gene expression. Adult stem cell-derived airway organoids can be used to elucidate early events of mycobacterial infection in human settings.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas, Valerio Iebba, Gerard Zalcman, Sylvie Friard, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, Francois Goldwasser, Carolina Alves Costa Silva, Safae Terrisse, Melodie Bonvalet, Arnaud Scherpereel, Herve Pegliasco, Corentin Richard, Francois Ghiringhelli, Arielle Elkrief, Antoine Desilets, Felix Blanc-Durand, Fabio Cumbo, Aitor Blanco, Romain Boidot, Sandy Chevrier, Romain Daillere, Guido Kroemer, Laurie Alla, Nicolas Pons, Emmanuelle Le Chatelier, Nathalie Galleron, Hugo Roume, Agathe Dubuisson, Nicole Bouchard, Meriem Messaoudene, Damien Drubay, Eric Deutsch, Fabrice Barlesi, David Planchard, Nicola Segata, Stephanie Martinez, Laurence Zitvogel, Jean-Charles Soria, Benjamin Besse
Summary: In addition to PD-L1 expression, biomarkers for predicting the response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. This study found that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI treatment in NSCLC patients, independent of PD-L1 expression and other factors. The relative abundance of Akk in the gut microbiome may serve as a potential biomarker for patient stratification.
Review
Oncology
Celia Delahaye, Sarah Figarol, Anne Pradines, Gilles Favre, Julien Mazieres, Olivier Calvayrac
Summary: The article discusses the benefits and limitations of more effective treatments for lung cancer patients, as well as the emergence of resistance. It emphasizes the importance of understanding the mechanisms underlying DTP survival for developing therapeutic strategies.
Article
Oncology
Marie Wislez, Julien Mazieres, Armelle Lavole, Gerard Zalcman, Olivier Carre, Thomas Egenod, Raffaele Caliandro, Catherine Dubos-Arvis, Gaelle Jeannin, Olivier Molinier, Marie-Ange Massiani, Alexandra Langlais, Franck Morin, Francoise Le Pimpec Barthes, Laurent Brouchet, Jalal Assouad, Bernard Milleron, Diane Damotte, Martine Antoine, Virginie Westeel
Summary: This study assessed the feasibility of neoadjuvant durvalumab for early-stage resectable non-small-cell lung cancer. The results showed that this treatment approach resulted in a high complete resection rate and some pathological response. However, the unexpectedly high postoperative mortality rate led to the premature termination of the study.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Silvia Novello, Dariusz M. Kowalski, Alexander Luft, Mahmut Gumus, David Vicente, Julien Mazieres, Jeronimo Rodriguez-Cid, Ali Tafreshi, Ying Cheng, Ki Hyeong Lee, Alexander Golf, Shunichi Sugawara, Andrew G. Robinson, Balazs Halmos, Erin Jensen, Paul Schwarzenberger, M. Catherine Pietanza, Luis Paz-Ares
Summary: This study provides five-year efficacy and safety outcomes for the treatment of previously untreated metastatic squamous non-small cell lung cancer patients. The results show that pembrolizumab plus chemotherapy significantly improves overall survival and progression-free survival compared to placebo plus chemotherapy. This study demonstrates that pembrolizumab plus chemotherapy is a first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Julien Mazieres, Helene Vioix, Boris M. Pfeiffer, Rhiannon I. Campden, Zhiyuan Chen, Bart Heeg, Alexis B. Cortot
Summary: METex14 skipping is a rare oncogenic driver in non-small-cell lung cancer and targeted therapy with MET tyrosine kinase inhibitors has been approved for its treatment. A systematic literature review found that the median frequency of METex14 skipping was 2.0% in unselected NSCLC patients and 2.4% in adenocarcinoma or nonsquamous subgroups. MET TKIs appeared to have higher efficacy outcomes for METex14 skipping NSCLC patients, but direct comparisons with chemotherapy or immunotherapy regimens were lacking.
CLINICAL LUNG CANCER
(2023)
Meeting Abstract
Oncology
Anne Pradines, Celine Callens, Aurelia Doussine, Ivan Bieche, Jerome Lemonnier, Marjorie Mauduit, Thomas Bachelot, Florence Dalenc, Alain Lortholary, Barbara Pistilli, Thibault De la Motte Rouge, Renaud Sabatier, Jean-Marc Ferrero, Sylvain Ladoire, Frederique Berger, Francois-Clement Bidard