Review
Cell Biology
Emma-Anne Karlsen, Sam Kahler, Joan Tefay, Shannon R. Joseph, Fiona Simpson
Summary: This review critically analyzes the mechanisms of EGFR expression in NSCLC, its relevance to currently approved targeted treatment options, and the complex nature of secondary mutations and intrinsic and acquired resistance patterns in NSCLC.
Article
Biochemistry & Molecular Biology
Yumiko Tahira, Katsuya Sakai, Hiroki Sato, Ryu Imamura, Kunio Matsumoto
Summary: The researchers found that the residues N127, V140, and K144 at the NK1 dimer interface play important roles in Met activation by HGF. Mutant NK1 proteins with alanine replacements at these residues lost their ability to activate Met, while mutant HGF proteins with the same replacements retained their activity, suggesting a distinction in the structural basis for NK1-dependent Met dimer formation and HGF-dependent Met activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Roya Mirzaei, Soodabeh Shafiee, Rana Vafaei, Malihe Salehi, Neda Jalili, Zahra Nazerian, Ahad Muhammadnajad, Fatemeh Yadegari, Mohamad Reza Esmailinejad, Leila Farahmand
Summary: Researchers successfully cloned and expressed an anti-EpCAM scFv antibody for breast cancer treatment. The recombinant antibody showed specific binding to malignant breast cancer cells and inhibited their migration and invasion ability. In vivo experiments with mouse models showed significant suppression of tumor growth and reduction in blood supply in response to the recombinant antibody intervention. These findings suggest that the antibody could be a therapeutic tool for reducing invasion and proliferation in malignant breast cancer.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Jazlyn P. Borges, Katrina Mekhail, Gregory D. Fairn, Costin N. Antonescu, Benjamin E. Steinberg
Summary: Chronic pain is a major public health issue that is often resistant to conventional analgesics. Recent studies have implicated the epidermal growth factor receptor (EGFR) signaling pathway in chronic pain, suggesting potential therapeutic targets for this devastating condition.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biology
Yongjian Huang, Jana Ognjenovic, Deepti Karandur, Kate Miller, Alan Merk, Sriram Subramaniam, John Kuriyan
Summary: Research has shown that the EGFR receptor can adopt different conformations of the extracellular module when binding to different ligands, with implications for intracellular signaling pathways.
Article
Chemistry, Multidisciplinary
Paolo Zucchiatti, Giovanni Birarda, Andrea Cerea, Marta S. Semrau, Aliaksandr Hubarevich, Paola Storici, Francesco De Angelis, Andrea Toma, Lisa Vaccari
Summary: This study demonstrates the potential of SEIRA microscopy in detecting subtle secondary structure modifications associated with the binding of Lapatinib to EGFR. By optimizing techniques and data analysis, the researchers successfully identified secondary structure modifications in EGFR related to a few amino acids.
Article
Oncology
Rana Vafaei, Zohreh Khaki, Malihe Salehi, Neda Jalili, Mohammad Reza Esmailinejad, Ahad Muhammadnajad, Seyed Mahdi Nassiri, Alireza Vajhi, Shima Moradi Kalbolandi, Roya Mirzaei, Leila Farahmand
Summary: In this study, a novel anti-MET scFv was designed and synthesized, which effectively suppressed the growth of MET-overexpressing breast cancer tumors.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Biochemistry & Molecular Biology
Thushara W. Madanayake, Eric A. Welsh, Lancia N. F. Darville, John M. Koomen, Charles E. Chalfant, Eric B. Haura, Timothy J. Robinson
Summary: We have developed a novel method to inhibit EGFR signaling using custom ASOs to induce exon skipping and drive the expression of dominant negative mRNA isoforms of EGFR. Our in vivo experiments showed that ASOs were highly effective in inhibiting colony formation, cell viability, and migration in EGFR mutant NSCLC. Importantly, ASOs maintained their efficacy in erlotinib-resistant subclones and wild-type EGFR overexpressing models, where erlotinib had no significant effect. By directly targeting the EGFR kinase domain, ASOs resulted in maximal inhibition of EGFR phosphorylation and downstream signaling in both EGFR mutant and erlotinib-resistant cells. Furthermore, our study confirmed the EGFR-specific therapeutic mechanism of ASOs in EGFR-independent NSCLC models. Further investigation of the synergy between ASOs and existing tyrosine kinase inhibitors could provide new clinical models to improve EGFR-targeted therapies for NSCLC patients, both mutant and wild-type.
NUCLEIC ACID THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Chao Wang, Yujing Zhang, Tingting Zhang, Jiazhen Xu, Saisai Yan, Bing Liang, Dongming Xing
Summary: Overexpression of EGFR has been linked to various cancers, and drug resistance caused by EGFR mutations is a significant challenge. EGFR dual-target inhibitors show promise in overcoming drug resistance and have higher efficacy compared to single-target inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Oncology
Ying-Yi Chen, Kuan-Hsun Lin, Yen-Shou Kuo, Yuan-Ming Tsai, Hsu-Kai Huang, Tsai-Wang Huang
Summary: This study investigated the impact of EGFR-TKI in patients with advanced lung adenocarcinoma treated with various therapeutic strategies. The results showed that TKI with lung cancer salvage surgery is the best therapeutic strategy, leading to significantly longer overall survival and extended duration of TKI usage.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Sojung Park, Sung Yong Lee, Dojin Kim, Yun Su Sim, Jeong-Seon Ryu, Juwhan Choi, Su Hwan Lee, Yon Ju Ryu, Jin Hwa Lee, Jung Hyun Chang
Summary: This study investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations and evaluated the efficacy of afatinib, erlotinib, and gefitinib according to mutation type. E19del and L858R mutations were associated with superior progression-free survival and overall survival compared to uncommon mutations. Afatinib showed significantly longer progression-free survival across all EGFR mutation types.
Article
Medicine, Research & Experimental
Allison S. Thomas, Carolyn Coote, Yvetane Moreau, John E. Isaac, Alexander C. Ewing, Athena P. Kourtis, Manish Sagar
Summary: This study examines the transmission of HIV-1 from mothers to infants and the role of antibody-dependent cellular cytotoxicity (ADCC) in preventing transmission. The findings suggest that infants exposed to more ADCC-susceptible strains and higher pretransmission ADCCBP are less likely to acquire HIV-1. Higher preexisting infant neutralization BP and greater maternal virus neutralization sensitivity do not associate with transmission.
Article
Medicine, General & Internal
Ning Liu, Lingnan Zheng, Min Yu, Shuang Zhang
Summary: This case report describes a patient with EGFR-mutant lung adenocarcinoma coexisting with pulmonary tuberculosis. The patient was initially diagnosed with pneumonia-like pulmonary adenocarcinoma and later confirmed to have active tuberculosis. The patient received a combination therapy of gefitinib and anti-TB treatment, leading to stable disease status and survival.
Article
Cell Biology
Faten Abdelli, Karim Jellali, Estefania Anguita, Maria Gonzalez-Munoz, Eduardo Villalobo, Ivan Madronal, Juan Alcalde, Mamdouh Ben Ali, Jihene Elloumi-Mseddi, Ikram Jemel, Francesc Tebar, Carlos Enrich, Sami Aifa, Antonio Villalobo
Summary: The study shows that EGFR with CaM-BD and CaM-LD domains affects the receptor's TK activity. Different EGFR mutants exhibit varying abilities to bind EGF, localize to the plasma membrane, and undergo ligand-dependent internalization.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Oncology
Lijuan Zhang, Meng Tian, Jiamao Lin, Jianbo Zhang, Haiyong Wang, Zhenxiang Li
Summary: The interaction between ER beta 1 and ER beta 5 in lung adenocarcinoma affects non-genomic signaling and resistance to EGFR TKIs. Cytoplasmic ER beta 1 may contribute to EGFR TKI resistance, and PC9/ER beta 1/5 cells show higher resistance to gefitinib.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Massimo Alfano, Irene Locatelli, Cristina D'Arrigo, Marco Mora, Giovanni Vozzi, Aurora De Acutis, Roberta Pece, Sara Tavella, Delfina Costa, Alessandro Poggi, Maria Raffaella Zocchi
Summary: This study reveals that increased stiffness and altered architecture of the extracellular matrix (ECM) are detectable in human lymphomas, and these modifications are related to the type and grading of the lymphoma. The findings suggest that digital pathology may assist in the diagnosis and treatment of lymphomas.
Review
Oncology
Alessandro Poggi, Maria Raffaella Zocchi
Summary: The discovery of immune checkpoints and the development of specific blockers have revolutionized anti-cancer therapy. This review focuses on the potential of NK ICs as targets for dual-checkpoint inhibition, highlighting their role in NK cell survival and anti-tumor immune response.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Oncology
Francesca Piaggio, Michela Croce, Francesco Reggiani, Paola Monti, Cinzia Bernardi, Marianna Ambrosio, Barbara Banelli, Mehmet Dogrusoez, Ralf Jockers, Domenico Bordo, Roberto Puzone, Silvia Viaggi, Domenico Coviello, Francesco B. Lanza, Martina Bartolucci, Andrea Petretto, Carlo Mosci, Rosaria Gangemi, Pieter A. van der Velden, Martine J. Jager, Ulrich Pfeffer, Adriana Amaro
Summary: This study investigated the impact of GNAQ and GNA11 gene mutations on the characteristics and prognosis of uveal melanoma. The results showed that GNA11 mutation was associated with worse prognosis and high-risk cytogenetic, mutational, and molecular tumor characteristics. Additionally, G-proteins encoded by GNAQ and GNA11 had different protein interaction partners, and differential DNA methylation might contribute to different progression risks.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Allergy
Arinna Bertoni, Federica Penco, Hilaria Mollica, Paola Bocca, Ignazia Prigione, Anna Corcione, Davide Cangelosi, Francesca Schena, Genny Del Zotto, Adriana Amaro, Noemi Paladino, Emanuele Pontali, Marcello Feasi, Sara Signa, Marta Bustaffa, Roberta Caorsi, Serena Palmeri, Paola Contini, Raffaele De Palma, Ulrich Pfeffer, Paolo Uva, Anna Rubartelli, Marco Gattorno, Stefano Volpi
Summary: This study reveals the crucial role of IL-1 beta in driving inflammatory phenotypes in severe COVID-19 patients, whose maturation and secretion are regulated by inflammasomes. The findings suggest that targeting IL-1 beta could be an effective strategy for treating COVID-19 and provide a mechanistic explanation for the strong inflammatory manifestations associated with the disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Editorial Material
Oncology
Serena Matis, Alessandro Poggi, Roberto Benelli
Editorial Material
Oncology
Roberto Benelli, Maria Raffaella Zocchi, Alessandro Poggi
Article
Oncology
Adriana Agnese Amaro, Rosaria Gangemi, Laura Emionite, Patrizio Castagnola, Gilberto Filaci, Martine. J. J. Jager, Enrica Teresa Tanda, Francesco Spagnolo, Matteo Mascherini, Ulrich Pfeffer, Michela Croce
Summary: It has been found that driver mutations GNAQ and GNA11 activate MAP kinase and YAP/TAZ pathways, and MEK inhibitors do not effectively block UM progression. Combined treatment of trametinib and different drugs targeting YAP/TAZ can overcome resistance. The combined treatment of trametinib and cerivastatin can inhibit the growth of BAP1 mutated and chromosome 3 monosomic uveal melanoma cell lines in vitro and in vivo.
Editorial Material
Oncology
Roberto Benelli, Maria Raffaella Zocchi, Alessandro Poggi
Article
Cell Biology
Delfina Costa, Roberta Vene, Simona Coco, Luca Longo, Francesca Tosetti, Stefano Scabini, Luca Mastracci, Federica Grillo, Alessandro Poggi, Roberto Benelli
Summary: The p38 inhibitor SB202190 is an essential component of normal colorectal mucosa cultures. It has been found that this molecule can stabilize EGFR signaling and promote organoid proliferation by increasing phosphorylation of Erk1-2. However, the growth of some colorectal cancer-derived organoid cultures is inhibited by SB202190 through an unknown mechanism.
Editorial Material
Oncology
Adriana Amaro, Ulrich Pfeffer
Article
Biochemistry & Molecular Biology
Francesco Reggiani, Marianna Ambrosio, Michela Croce, Enrica Teresa Tanda, Francesco Spagnolo, Edoardo Raposio, Mariangela Petito, Zeinab El Rashed, Alessandra Forlani, Ulrich Pfeffer, Adriana Agnese Amaro
Summary: The metastatic risk of uveal melanoma (UM) is determined by limited molecular lesions, somatic mutations, and copy number alterations. BAP1 mutations are always associated with M3 in high-risk patients, while other features such as 6p, 8q, M3, and SF3B1 mutation are present independently. Chr8q gain is frequently associated with chr3 disomy. Gene expression data analysis reveals two clusters, one enriched in metastatic samples with 8q|M3, BAP1|M3, and the other mainly containing low-risk samples with 6p combined with either 8q or SF3B1. Some gene expression events become significant when considering combinations of risk features, indicating additive action. The independence of risk factors supports a random risk model of UM metastasis without an obligatory sequence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Diego de Miguel-Perez, Edward M. Pickering, Umberto Malapelle, William Grier, Francesco Pepe, Pasquale Pisapia, Gianluca Russo, Joseph A. Pinto, Alessandro Russo, Giancarlo Troncone, Melissa J. Culligan, Katherine A. Scilla, Ranee Mehra, Pranshu Mohindra, Oscar Arrieta, Andres F. Cardona, Marzia Del Re, Ashutosh Sachdeva, Fred R. Hirsch, Andrea Wolf, Joseph S. Friedberg, Christian Rolfo
Summary: In this study, genetic alterations in resectable pleural mesothelioma tissues and blood samples were analyzed, and it was found that high tissue tumor mutational burden, tissue median minor allele frequency, blood tumor mutational burden, and specific mutations were correlated with outcomes in patients with resected PM. These findings suggest that molecular profiling could help identify longer survivors in patients with resected PM.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Davide Melisi, Camilla Zecchetto, Valeria Merz, Giuseppe Malleo, Luca Landoni, Alberto Quinzii, Simona Casalino, Federica Fazzini, Marina Gaule, Camilla Pesoni, Luca Casetti, Alessandro Esposito, Giovanni Marchegiani, Cristiana Piazzola, Mirko D'Onofrio, Riccardo de Robertis, Armando Gabbrielli, Laura Bernardoni, Stefano F. Crino, Silvia Pietrobono, Claudio Luchini, Camillo Aliberti, Guido Martignoni, Stefano Milleri, Giovanni Butturini, Aldo Scarpa, Roberto Salvia, Claudio Bassi
Summary: This study evaluated the safety and activity of liposomal irinotecan in the perioperative treatment of resectable pancreatic ductal adenocarcinoma (rPDAC) patients. The results showed that NALIRIFOX has manageable and active outcomes, and should be further investigated in randomized trials comparing it to standard upfront surgery followed by adjuvant therapy.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Eric Jonasch, Todd M. Bauer, Kyriakos P. Papadopoulos, Elizabeth R. Plimack, Jaime R. Merchan, David F. Mcdermott, M. Dror Michaelson, Leonard J. Appleman, Ananya Roy, Rodolfo F. Perini, Yanfang Liu, Toni K. Choueiri
Summary: After a median follow-up of 41.2 months, belzutifan monotherapy demonstrated durable antitumor activity in patients with advanced ccRCC and acceptable safety.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Patricia A. H. Hamers, Geraldine R. Vink, Marloes A. G. Elferink, Leon M. G. Moons, Cornelis J. A. Punt, Anne M. May, Miriam Koopman
Summary: Screen-detection of the primary tumor is associated with longer overall survival after metachronous metastasis.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Camilla Nero, Nicolo Bizzarri, Stefano Di Berardino, Francesca Sillano, Giuseppe Vizzielli, Francesco Cosentino, Virginia Vargiu, Pierandrea De Iaco, Anna Myriam Perrone, Enrico Vizza, Benito Chiofalo, Stefano Uccella, Fabio Ghezzi, Luigi Carlo Turco, Giacomo Corrado, Diana Giannarelli, Tina Pasciuto, Gian Franco Zannoni, Anna Fagotti, Giovanni Scambia
Summary: This study evaluates the sensitivity and specificity of sentinel-lymph-node mapping compared to systematic lymphadenectomy in detecting lymph node metastasis in early stage ovarian cancer. The results show that sentinel-lymph-node mapping did not reach the expected sensitivity, but ultra-staging protocol improved the accuracy of diagnosis for patients.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Adriana Hepner, Judith M. Versluis, Roslyn Wallace, Clara Allayous, Lauren Julia Brown, Claudia Trojanielloh, Camille Lea Gerardi, Yanina J. L. Jansenj, Prachi Bhave, Bart Neyns, Andrew Haydon, Olivier Michielin, Joanna Manganan Oliver Klein, Alexander N. Shoushtari, Allison Betof Warner, Paolo Antonio Ascierto, Jennifer Leigh McQuade, Matteo S. Carlino, Lisa Zimmer, Celeste Lebbe, Douglas B. Johnson, Shahneen Sandhu, Victoria Atkinson, Christian U. Blank, Serigne N. Lo, Georgina V. Long, Alexander M. Menzies
Summary: Acquired resistance to PD-1 therapy in melanoma is mainly oligometastatic, and patients may have a favorable survival outcome following salvage treatment.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Savannah Roy, Stephanie Lakritz, Anna R. Schreiber, Elizabeth Molina Kuna, Cathy J. Bradley, Lavanya Kondapalli, Jennifer R. Diamond
Summary: This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with anthracycline and taxane-based chemotherapy (ATAX) compared to taxane-based chemotherapy (TAX). The results show that ATAX does not increase the risk of MACE and there is no difference in survival between patients who received TAX and ATAX.
EUROPEAN JOURNAL OF CANCER
(2024)
Letter
Oncology
Pei-Chun Weng, Yau-Li Huang, Chun-Yu Cheng
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Philipp Jansen, Jean Le 'Clerc Arrastia, Daniel Otero Baguer, Maximilian Schmidt, Jennifer Landsberg, Joerg Wenzel, Michael Emberger, Dirk Schadendorf, Eva Hadaschik, Peter Maass, Klaus Georg Griewank
Summary: This study highlights the enormous potential of artificial intelligence in pathology, showing that it can aid in the identification of rare cutaneous adnexal tumors and potentially become a standard tool in routine diagnostics.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Casper W. F. van Eijck, Gaby Strijk, Eveline E. Vietscha, Fleur van der Sijde, Maaike Verheij, Dana A. M. Mustafa, Madelief Vinkc, Joachim G. J. V. Aerts, Casper H. J. van Eijck, Marcella Willemsen
Summary: The study reveals that FOLFIRINOX has immunomodulatory effects, suggesting its potential in immune-based combination therapies for pancreatic cancer. Additionally, certain plasma proteins hold promise as circulating predictive biomarkers for early prediction of FOLFIRINOX response in patients with pancreatic cancer.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Marwan Fakih, Chongkai Wang, Jaideep Sandhu, Jian Ye, Colt Egelston, Xiaochen Li
Summary: This study explores the impact of metastatic sites on treatment outcomes for chemotherapy-refractory colorectal cancer patients. It found that patients with liver or peritoneal metastases had poor treatment outcomes, while those with lung-only metastases showed significant response. The presence of concurrent lymph node or other extrahepatic metastatic disease diminished treatment response in patients with lung metastases. Future checkpoint inhibitor trials should stratify patients based on metastatic locations.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Georgios Christos Tsiatsianis, Candace S. Y. Chan, Ioannis Mouratidis, Nikol Chantzi, Anna Maria Tsiatsiani, Nelson S. Yee, Apostolos Zaravinos, Verena Kantere, Ilias Georgakopoulos-Soares
Summary: The study reveals that nullpeptides can serve as biomarkers for cancer detection and treatment, particularly in highly recurrent cancer patients. These nullpeptides primarily occur in highly expressed genes, particularly in specific loci of oncogenes and tumor suppressors. Recurrent nullpeptides are more likely to be found in neoantigens, which play a significant role in immunotherapy.
EUROPEAN JOURNAL OF CANCER
(2024)