Editorial Material
Oncology
Sun Min Lim, Chang Gon Kim, Byoung Chul Cho
Summary: Treatment resistance to targeted agents is a significant challenge in cancer therapy and is also observed in EGFR-mutant NSCLC. Current efforts focus on delaying or overcoming acquired resistance, and targeting compensatory feedback loops along with oncogenic signaling pathways holds promise for improved outcomes.
Article
Cell Biology
Ke-Ren Zhang, Yu-Fei Zhang, Hui-Min Lei, Ya-Bin Tang, Chun-Shuang Ma, Qian-Ming Lv, Shi-Yi Wang, Li-Ming Lu, Ying Shen, Hong-Zhuan Chen, Liang Zhu
Summary: The study uncovered a metabolic mechanism driving resistance to EGFR TKIs by promoting cystine metabolism, and suggested AKR1B1 as a potential therapeutic target to overcome resistance to EGFR TKIs.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biophysics
Parimala Devi Ganthala, Sateesh Alavala, Naveen Chella, Sai Balaji Andugulapati, Nagendra Babu Bathini, Ramakrishna Sistla
Summary: Erlotinib-based EGFR targeted therapy has shown significant clinical improvement against non-small cell lung cancer. However, the development of drug resistance limits its effectiveness. In this study, the combination of Erlotinib and Quercetin was found to be more synergistic against certain lung cancer cells compared to other natural products. By preparing drug-loaded nanoparticles, the encapsulation efficiency and release performance of the drugs were improved. The nanoparticles could reduce the expression of drug-resistant proteins, increase drug uptake, and induce apoptosis in drug-resistant cells. In vivo experiments also showed increased uptake of nanoparticles in lung tissue and decreased expression of cancer-related genes.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Biology
Xiaolong Tang, Lizhi Cheng, Guo Li, Yong-Ming Yan, Fengting Su, Dan-Ling Huang, Shuping Zhang, Zuojun Liu, Minxian Qian, Ji Li, Yong-Xian Cheng, Baohua Liu
Summary: The small molecule compound D6 demonstrates promising efficacy in treating EGFR-TKI resistant NSCLC by targeting the protein-protein interaction between HSP90 and T790M-EGFR, offering a potential alternative strategy to overcome drug resistance.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Irlanda Peralta-Arrieta, Octavio A. Trejo-Villegas, Leonel Armas-Lopez, Hugo A. Ceja-Rangel, Maria Del Carmen Ordonez-Luna, Priscila Pineda-Villegas, Marco A. Gonzalez-Lopez, Blanca Ortiz-Quintero, Criselda Mendoza-Milla, Zyanya L. Zatarain-Barron, Oscar Arrieta, Joaquin Zuniga, Federico Avila-Moreno
Summary: The study found that overexpression of MEOX2/GLI1 in lung cancer cells is associated with the activation of EGFR/AKT/ERK signaling pathway and aberrant epigenetic modulation of the EGFR gene. These findings suggest that MEOX2/GLI1 may play a crucial role in mediating resistance to cisplatin and EGFR-TKI-based therapy in lung cancer cells.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Przemyslaw Bieganski, Martina Godel, Chiara Riganti, Daniel Fabio Kawano, Joanna Kopecka, Konrad Kowalski
Summary: A library of 1,4- and 1,5-triazole ferrocenyl derivatives of erlotinib were synthesized and their anticancer activity was studied against erlotinib-sensitive and erlotinib-resistant lung cancer cells. Among the compounds investigated, two isomers showed superior activity against erlotinib-resistant cells, with a mechanism of action different from erlotinib.
BIOORGANIC CHEMISTRY
(2022)
Article
Oncology
Shiyao Jiang, Jingjing Huang, Hua He, Yueying Liu, Lu Liang, Xiaoyan Sun, Yi Li, Li Cong, Bei Qing, Yiqun Jiang
Summary: This study investigated the relationship between erlotinib resistance and stemness in lung adenocarcinoma. The key gene NCAPG2 was identified as playing a vital role in both stemness and erlotinib resistance in lung adenocarcinoma. These findings provide important insights for the treatment and prognosis of patients with lung adenocarcinoma.
Article
Medicine, Research & Experimental
Hongqiao Cai, Ruobing Wang, Xingren Guo, Meiyu Song, Fei Yan, Bai Ji, Yahui Liu
Summary: The combination of gemcitabine-loaded PLGA nanoparticles with a macrophage membrane coating showed promising results in reducing drug toxicity, improving tumor accumulation, and inhibiting pancreatic cancer cell proliferation through targeting signaling pathways. This approach provides potential synergistic anti-tumor efficacy for treating pancreatic cancer.
MOLECULAR PHARMACEUTICS
(2021)
Article
Oncology
Alexis B. Cortot, Anne Madroszyk, Etienne Giroux-Leprieur, Olivier Molinier, Elisabeth Quoix, Henri Berard, Josiane Otto, Isabelle Rault, Denis Moro-Sibilot, Judith Raimbourg, Elodie Amour, Franck Morin, Jose Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Aldo Renault, Eric Pichon, Benjamin Huret, Sandrine Charpentier, Marc G. Denis, Jacques Cadranel
Summary: The addition of cetuximab to afatinib in the treatment of treatment-naive advanced EGFR-mutant NSCLC did not show any significant improvement in efficacy, suggesting that further investigation into this combination therapy may not be warranted.
CLINICAL CANCER RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Yun Hu, Sebastien Paris, Genevieve Bertolet, Hampartsoum B. Barsoumian, Kewen He, Duygu Sezen, Dawei Chen, Mark Wasley, Jordan Da Silva, Joylise A. Mitchell, Tiffany A. Voss, Fatemeh Masrorpour, Claudia Kettlun Leyton, Liangpeng Yang, Carola Leuschner, Nahum Puebla-Osorio, Saumil Gandhi, Quynh-Nhu Nguyen, Maria Angelica Cortez, James W. Welsh
Summary: This study successfully combined nanoparticle-enhanced radiotherapy with simultaneous blockade of multiple immune checkpoint receptors, effectively controlling tumor growth, enhancing animal survival, and destroying both tumors in approximately 30% of treated mice. This combinatorial therapy stimulates immune response and exhibits immunological memory response, demonstrating significant clinical potential.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
A. S. Pal, M. Bains, A. Agredo, A. L. Kasinski
Summary: Lung cancer is a major cause of cancer-related deaths, and overcoming resistance to EGFR inhibitors is crucial in the treatment of non-small cell lung cancer. This study identifies the important role of microRNAs in driving resistance to EGFR inhibitors in non-small cell lung cancer cells.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Oncology
Fabrice Barlesi, Pascale Tomasini, Maryam Karimi, Stefan Michiels, Judith Raimbourg, Catherine Daniel, Henri Janicot, Anne Madroszyk, Clarisse Audigier-Valette, Elisabeth Quoix, Julien Mazieres, Denis Moro-Sibilot, Eric Dansin, Olivier Molinier, Hugues Morel, Eric Pichon, Alexis Cortot, Josiane Otto, Francois Chomy, Pierre-Jean Souquet, Nicolas Cloarec, Etienne Giroux-Leprieur, Ivan Bieche, Ludovic Lacroix, Sandrine Boyault, Valery Attignon, Isabelle Soubeyran, Alain Morel, Alicia Tran-Dien, Alexandra Jacquet, Filippo Gustavo Dall'Olio, Marta Jimenez, Jean-Charles Soria, Benjamin Besse
Summary: Targeted therapies and immune checkpoint blockers have revolutionized the treatment of non-small cell lung cancer. This study investigated the use of targeted therapies and immune checkpoint blockers as maintenance therapy based on molecular characterization. The results showed no significant differences in progression-free survival between targeted therapies and standard-of-care, and immune checkpoint blockers showed enhanced benefits in patients with PD-L1 >= 1%.
CLINICAL CANCER RESEARCH
(2022)
Review
Immunology
Mohan Liu, Kaiwen Xiao, Li Yang
Summary: Immuno-combination therapy is emerging as an effective treatment for advanced non-small cell lung carcinoma (NSCLC). However, compared to monotherapy, such as monoclonal antibodies or kinase inhibitors, whether combination therapy can enhance antitumor efficacy or alleviate side effects remains unclear.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ebony Nottingham, Elizabeth Mazzio, Sunil Kumar Surapaneni, Shallu Kutlehria, Arindam Mondal, Ramesh Badisa, Stephen Safe, Arun K. Rishi, Mandip Singh
Summary: The study demonstrates that CDODA-Me can enhance the sensitivity of ERL-resistant NSCLC cells to ERL, leading to synergistic therapeutic effects through inhibition of mitosis and induction of oxidative stress.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Article
Cell Biology
Oliver H. Voss, Daniel Arango, Justin C. Tossey, Miguel A. Villalona Calero, Andrea Doseff
Summary: Apigenin sensitizes primary lung cancer cells to TRAIL-induced apoptosis through reprogramming alternative splicing of key TRAIL/DISC components and directly binding heat shock protein 70 to promote cell death. These findings emphasize the synergies between diet and cancer treatments, providing new avenues for improved cancer therapies.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Lorena Landuzzi, Arianna Palladini, Claudio Ceccarelli, Sofia Asioli, Giordano Nicoletti, Veronica Giusti, Francesca Ruzzi, Marianna L. Ianzano, Laura Scalambra, Roberta Laranga, Tania Balboni, Maddalena Arigoni, Martina Olivero, Raffaele A. Calogero, Carla De Giovanni, Massimiliano Dall'Ora, Enrico Di Oto, Donatella Santini, Maria Pia Foschini, Maria Cristina Cucchi, Simone Zanotti, Mario Taffurelli, Patrizia Nanni, Pier-Luigi Lollini
Summary: Through long-term in vivo passages in severely immunodeficient mice, a study on patient-derived xenografts (PDX) from human primary breast cancers showed stable biomarker expression and growth phenotype in most cases, but one HER2-positive PDX subline exhibited progressive tumor growth, resistance to cell senescence, increased stem cell marker expression, high metastatic ability, and decreased BCL2 expression. The study revealed potential connections between BCL2 and other down-regulated hub genes, suggesting a partial epithelial-to-mesenchymal transition in the progressed subline. The findings provide insights into breast cancer progression mechanisms and new therapeutic approaches.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Silvia La Monica, Claudia Fumarola, Daniele Cretella, Mara Bonelli, Roberta Minari, Andrea Cavazzoni, Graziana Digiacomo, Maricla Galetti, Francesco Volta, Maicol Mancini, Pier Giorgio Petronini, Marcello Tiseo, Roberta Alfieri
Summary: The study investigated the potential of abemaciclib as a second-line treatment after osimertinib resistance and the impact of combining it with osimertinib on overcoming resistance. Abemaciclib inhibits CDK4/6, showing inhibitory effects on cell growth and spheroid formation in resistant cell lines.
Article
Multidisciplinary Sciences
Diala Kantar, Emilie Bousquet Mur, Maicol Mancini, Vera Slaninova, Yezza Ben Salah, Luca Costa, Elodie Forest, Patrice Lassus, Charles Geminard, Florence Boissiere-Michot, Beatrice Orsetti, Charles Theillet, Jacques Colinge, Christine Benistant, Antonio Maraver, Lisa Heron-Milhavet, Alexandre Djiane
Summary: Loss of junctional scaffold protein MAGI1 is associated with poor prognosis in luminal breast cancer, promoting tumorigenesis through alterations in cell stiffness and signaling pathways. MAGI1 acts as a tumor suppressor in luminal breast cancer by inhibiting an AMOTL2/p38 stress pathway.
SCIENTIFIC REPORTS
(2021)
Correction
Cell Biology
Ayse Ertay, Huiquan Liu, Dian Liu, Ping Peng, Charlotte Hill, Hua Xiong, David Hancock, Xianglin Yuan, Marcin R. Przewloka, Mark Coldwell, Michael Howell, Paul Skipp, Rob M. Ewing, Julian Downward, Yihua Wang
CELL DEATH & DISEASE
(2021)
Article
Oncology
Maicol Mancini, Quentin-Dominique Thomas, Sylvia Bourdel, Laura Papon, Emilie Bousquet, Prisca Jalta, Silvia La Monica, Camille Travert, Roberta Alfieri, Xavier Quantin, Marta Canamero, Antonio Maraver
Summary: The use of targeted therapy has improved the clinical management of lung cancer patients, but resistance remains a common issue. Combining different therapies may help delay or eliminate the development of resistance.
Article
Medicine, Research & Experimental
E. Josue Ruiz, Linxiang Lan, Markus Elmar Diefenbacher, Eva Madi Riising, Clive Da Costa, Atanu Chakraborty, Joerg D. Hoeck, Bradley Spencer-Dene, Gavin Kelly, Jean-Pierre David, Emma Nye, Julian Downward, Axel Behrens
Summary: In a mouse model of K-RasG12D-induced lung adenocarcinoma, deletion or mutation of c-Jun unexpectedly increased lung tumor burden, while the Jun family member JunD was found to be crucial in JNK signaling and Ras-induced lung cancer in the absence of c-Jun.
Article
Oncology
Giulia Golinelli, Giulia Grisendi, Massimiliano Dall'Ora, Giulia Casari, Carlotta Spano, Rebecca Talami, Federico Banchelli, Malvina Prapa, Chiara Chiavelli, Filippo Rossignoli, Olivia Candini, Roberto D'Amico, Milena Nasi, Andrea Cossarizza, Livio Casarini, Massimo Dominici
Summary: The study demonstrates that bi-functional MSCs expressing TRAIL and GD2 tCAR can effectively target and kill ES tumor cells, showing good efficacy in targeting and eliminating ES in the lungs but not in the liver.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Febe van Maldegem, Karishma Valand, Megan Cole, Harshil Patel, Mihaela Angelova, Sareena Rana, Emma Colliver, Katey Enfield, Nourdine Bah, Gavin Kelly, Victoria Siu Kwan Tsang, Edurne Mugarza, Christopher Moore, Philip Hobson, Dina Levi, Miriam Molina-Arcas, Charles Swanton, Julian Downward
Summary: This study introduces a workflow for studying the TME in mouse models using imaging mass cytometry, allowing for optimized image segmentation strategies and automated processes for parallel segmentation of large multi-image datasets.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Tereza Vaclova, Atanu Chakraborty, James Sherwood, Sarah Ross, Danielle Carroll, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: The study investigates the co-occurrence of additional KRAS mutations with KRAS G12C in non-small cell lung cancer (NSCLC) tumors and its impact on cellular response to G12C-specific inhibitors. The results show that KRAS c.35G>T mutation most frequently co-occurred with KRAS G12C and led to cellular resistance to G12C inhibitors. Therefore, comprehensive genotyping of KRAS tumors is necessary for optimal patient selection for treatment with a KRAS G12C inhibitor.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Malvina Prapa, Chiara Chiavelli, Giulia Golinelli, Giulia Grisendi, Marco Bestagno, Rosanna Di Tinco, Massimiliano Dall'Ora, Giovanni Neri, Olivia Candini, Carlotta Spano, Tiziana Petrachi, Laura Bertoni, Gianluca Carnevale, Giuseppe Pugliese, Roberta Depenni, Alberto Feletti, Corrado Iaccarino, Giacomo Pavesi, Massimo Dominici
Summary: The study revealed that GD2 CAR has strong anti-tumor potential in glioblastoma models, and intracerebral CAR T injection significantly increased survival time without any side effects.
NPJ PRECISION ONCOLOGY
(2021)
Editorial Material
Medicine, General & Internal
Miriam Molina-Arcas, Julian Downward
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Philip East, Gavin P. Kelly, Dhruva Biswas, Michaela Marani, David C. Hancock, Todd Creasy, Kris Sachsenmeier, Charles Swanton, Julian Downward, Sophie de Carne Trecesson
Summary: The study found that 84% of patients with lung adenocarcinoma have oncogenic activation of the RAS signaling pathway, with a high proportion of activation even in KRAS wild-type tumors; patient groups with high RAS activity show adverse clinical outcomes and reduced response to chemotherapy. Stratifying patients based on oncogenic RAS transcriptional activity may ultimately assist in clinical decision-making.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
May Zaw Thin, Christopher Moore, Thomas Snoeks, Tammy Kalber, Julian Downward, Axel Behrens
Summary: In this paper, a method of lung nodule image acquisition and analysis using a micro-computed tomography scanner is introduced for translational research in lung cancer that closely mimics clinical environments. The method has the advantages of low radiation dose, high resolution, and high-throughput imaging, and utilizes specific image analysis tools for identifying different types of lung tumors.
Article
Oncology
Massimiliano Dall'Ora, Giulia Rovesti, Luca Reggiani Bonetti, Giulia Casari, Federico Banchelli, Luca Fabbiani, Elena Veronesi, Tiziana Petrachi, Paolo Magistri, Fabrizio Di Benedetto, Andrea Spallanzani, Chiara Chiavelli, Maria Carlotta Spano, Antonino Maiorana, Massimo Dominici, Giulia Grisendi
Summary: This study assessed the expression of TRAIL receptors in PDAC tumor tissue and stromal cells, finding that functional receptors were widely expressed and represented a promising treatment target. Low expression of decoy receptors in primary PDAC tumor cells was associated with a poor prognosis. A cellular-dense tumor stroma in PDAC was linked to reduced relapse-free survival.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Huizhong Xiong, Maicol Mancini, Michael Gobert, Shiqian Shen, Glaucia C. Furtado, Sergio A. Lira, Christopher N. Parkhurst, Veronique Garambois, Muriel Brengues, Carlos E. Tadokoro, Thomas Trimarchi, Gonzalo Gomez-Lopez, Amartya Singh, Hossein Khiabanian, Sonia Minuzzo, Stefano Indraccolo, Camille Lobry, Iannis Aifantis, Daniel Herranz, Juan J. Lafaille, Antonio Maraver
Summary: The study revealed that Notch pathway activity in T-ALL depends on DLL4 signaling, while the spleen plays a major role in DLL4-driven T-ALL.