Article
Oncology
Xiyin Li, Hairui Wang, Xing Yang, Xiaoqi Wang, Lina Zhao, Li Zou, Qin Yang, Zongliu Hou, Jing Tan, Honglei Zhang, Jianyun Nie, Baowei Jiao
Summary: Through research, it was found that GABRP can sustain the stemness of TNBC by modulating EGFR expression, affecting sensitivity to chemotherapy drugs, indicating that GABRP may be a potential therapeutic target.
Article
Medicine, Research & Experimental
Hui Hua, Jiajia Zeng, Haixin Xing, Yuxin He, Linyu Han, Nasha Zhang, Ming Yang
Summary: This study systematically evaluated the role of genetic variants in A-to-I editing genes on the prognosis of NSCLC patients receiving EGFR-TKIs therapy. The researchers identified several SNPs in the ADAR gene that were significantly associated with patient prognosis and found that silencing ADAR enhanced the sensitivity of NSCLC cells to gefitinib. These findings highlight the importance of A-to-I RNA editing in drug resistance and suggest ADAR as a potential therapeutic target for unresectable NSCLC.
Article
Oncology
Siang-Boon Koh, Kenneth Ross, Steven J. Isakoff, Nsan Melkonjan, Lei He, Karina J. Matissek, Andrew Schultz, Erica L. Mayer, Tiffany A. Traina, Lisa A. Carey, Hope S. Rugo, Minetta C. Liu, Vered Stearns, Adam Langenbucher, Srinivas Vinod Saladi, Sridhar Ramaswamy, Michael S. Lawrence, Leif W. Ellisen
Summary: This study identifies high levels of RASAL2 as predictors of chemotherapy response and long-term outcomes in TNBC. RASAL2 rewires MAPK feedback and cross-talk to confer resistance to MEK1/2 and EGFR inhibitors while also indicating sensitivity to these inhibitors.
CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Yuhong Liu, Xiaoyong Dai, Shengwei Jiang, Mulan Qahar, Chunyan Feng, Dongdong Guo, Lijun Wang, Shaohua Ma, Laiqiang Huang
Summary: The combination of rapamycin and gefitinib has been shown to enhance the therapeutic efficacy in overcoming gefitinib resistance in NSCLC. Additionally, targeted delivery of the drugs using an aptamer-nanoparticle carrier system further enhances the therapeutic efficacy of gefitinib.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Pinar Ozden Eser, Raymond M. Paranal, Jieun Son, Elena Ivanova, Yanan Kuang, Heidi M. Haikala, Ciric To, Jeffrey J. Okoro, Kshiti H. Dholakia, Jihyun Choi, Yoonji Eum, Atsuko Ogino, Pavlos Missios, Dalia Ercan, Man Xu, Michael J. Poitras, Stephen Wang, Kenneth Ngo, Michael Dills, Masahiko Yanagita, Timothy Lopez, Mika Lin, Jeanelle Tsai, Nicolas Floch, Emily S. Chambers, Jennifer Heng, Rana Anjum, Alison D. Santucci, Kesi Michael, Alwin G. Schuller, Darren Cross, Paul D. Smith, Geoffrey R. Oxnard, David A. Barbie, Lynette M. Sholl, Magda Bahcall, Sangeetha Palakurthi, Prafulla C. Gokhale, Cloud P. Paweletz, George Q. Daley, Pasi A. Janne
Summary: Some EGFR-mutant, MET-amplified lung cancers may develop dependence on MET activation alone, suggesting that these patients could be treated with a single-agent MET TKI instead of the current standard-of-care EGFR and MET inhibitor combination regimens.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Jung Hee Cho, Yeon-Mi You, Han Koo, Dong Chul Lee, Young Il Yeom, Kyung Chan Park
Summary: This study identified LPIN1 as a key factor in regulating gefitinib resistance in EGFR-mutant NSCLC cells, and found that LPIN1 expression was induced following gefitinib treatment, leading to increased lipid droplet formation and activation of protein kinase C delta and nuclear factor kappa B. Targeting LPIN1 was shown to synergistically inhibit tumor growth, suggesting a potential effective strategy for preventing TKI resistance in NSCLC patients.
Article
Multidisciplinary Sciences
Iris K. van Alderwerelt van Rosenburgh, David M. Lu, Michael J. Grant, Steven E. Stayrook, Manali Phadke, Zenta Walther, Sarah B. Goldberg, Katerina Politi, Mark A. Lemmon, Kumar D. Ashtekar, Yuko Tsutsui
Summary: This study investigates the molecular basis for the varying response of non-small cell lung cancers driven by EGFR mutations to tyrosine kinase inhibitors. The researchers identify structural features that contribute to inhibitor sensitivity and propose a classification system for predicting clinical outcomes.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jing Bi, Zhihui Wu, Xin Zhang, Taoling Zeng, Wanjun Dai, Ningyuan Qiu, Mingfeng Xu, Yikai Qiao, Lang Ke, Jiayi Zhao, Xinyu Cao, Qi Lin, Xiao Lei Chen, Liping Xie, Zhong Ouyang, Jujiang Guo, Liangkai Zheng, Chao Ma, Shiying Guo, Kangmei Chen, Wei Mo, Guo Fu, Tong-Jin Zhao, Hong-Rui Wang
Summary: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in TNBC progression. However, targeting EGFR using antibodies shows no significant benefits for TNBC patients. This study reveals that deficiency of TMEM25 allows EGFR monomer to activate STAT3 independent of ligand binding, promoting TNBC progression, and suggests TMEM25 as a potential targeted therapy for TNBC.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
T. L. Peters, T. Patil, A. T. Le, K. D. Davies, P. M. Brzeskiewicz, H. Nijmeh, L. Bao, D. R. Camidge, D. L. Aisner, R. C. Doebele
Summary: EGFR mutant non-small cell lung cancer patients initially respond well to EGFR-targeted therapy but often develop acquired resistance, which requires broad molecular testing to understand the resistance mechanisms and develop new treatment options.
NPJ PRECISION ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sk. Kayum Alam, Yongchang Zhang, Li Wang, Zhu Zhu, Christina E. Hernandez, Yuling Zhou, Nong Yang, Jian Lei, Xiaoyan Chen, Liang Zeng, Mark A. Klein, Luke H. Hoeppner
Summary: The study reveals that DARPP-32 and kinase-activated EGFR and ERBB3 proteins are overexpressed in EGFR TKI-refractory LUAD, leading to the evasion of cell death through a specific mechanism.
Article
Multidisciplinary Sciences
Hui Deng, Qian Lei, Chengdi Wang, Zhoufeng Wang, Hai Chen, Gang Wang, Na Yang, Dan Huang, Quanwei Yu, Mengling Yao, Xue Xiao, Guonian Zhu, Cheng Cheng, Yangqian Li, Feng Li, Panwen Tian, Weimin Li
Summary: In this study, the authors present a fluorescence-activated cell sorting assay to identify activating EGFR mutations in lung cancer patients and demonstrate its utility in predicting response to EGFR-tyrosine kinase inhibitors.
NATURE COMMUNICATIONS
(2022)
Review
Medicine, General & Internal
Tai-Huang Lee, Hsiao-Ling Chen, Hsiu-Mei Chang, Chiou-Mei Wu, Kuan-Li Wu, Chia-Yu Kuo, Po-Ju Wei, Chin-Ling Chen, Hui-Lin Liu, Jen-Yu Hung, Chih-Jen Yang, Inn-Wen Chong
Summary: Patients with advanced non-small cell lung cancer (NSCLC) who have susceptible epidermal growth factor receptor (EGFR) mutations and receive combination treatment with EGFR tyrosine kinase inhibitors (TKIs) and anti-angiogenic agents show better progression-free survival (PFS) outcomes, especially among patients with a smoking history or those treated with erlotinib-based therapy. Combination therapy significantly prolongs PFS regardless of ethnicity.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Ashish Noronha, Nishanth Belugali Nataraj, Joo Sang Lee, Benny Zhitomirsky, Yaara Oren, Sara Oster, Moshit Lindzen, Saptaparna Mukherjee, Rainer Will, Soma Ghosh, Arturo Simoni-Nieves, Aakanksha Verma, Rishita Chatterjee, Simone Borgoni, Welles Robinson, Sanju Sinha, Alexander Brandis, D. Lucas Kerr, Wei Wu, Arunachalam Sekar, Suvendu Giri, Youngmin Chung, Diana Drago-Garcia, Brian P. Danysh, Mattia Lauriola, Michelangelo Fiorentino, Andrea Ardizzoni, Moshe Oren, Collin M. Blakely, Jideofor Ezike, Stefan Wiemann, Laxmi Parida, Trever G. Bivona, Rami Aqeilan, Joan S. Brugge, Aviv Regev, Gad Getz, Eytan Ruppin, Yosef Yarden
Summary: EGFR inhibitors activate endogenous mutators in lung cancer cells, leading to drug resistance. Inhibiting this process can prevent drug resistance.
Article
Oncology
Aram Ko, Mohammad Hasanain, Young Taek Oh, Fulvio D'Angelo, Danika Sommer, Brulinda Frangaj, Suzanne Tran, Franck Bielle, Bianca Pollo, Rosina Paterra, Karima Mokhtari, Rajesh Kumar Soni, Matthieu Peyre, Marica Eoli, Laura Papi, Michel Kalamarides, Marc Sanson, Antonio Iavarone, Anna Lasorella
Summary: LZTR1 is a substrate-specific adaptor of a CUL3-dependent ubiquitin ligase frequently mutated in cancer. The study identified EGFR and AXL as LZTR1 substrates targeted for degradation, and found that LZTR1 mutations result in the accumulation and deregulated signaling of EGFR and AXL. The study also revealed vulnerabilities of LZTR1-mutant tumors to inhibition of EGFR and AXL, providing precision targeting for patients with LZTR1-mutant cancer.
Article
Multidisciplinary Sciences
Maria Gabriella Dona, Massimo Giuliani, Francesca Rollo, Maria Fenicia Vescio, Maria Benevolo, Amalie Giglio, Eugenia Giuliani, Aldo Morrone, Alessandra Latini
Summary: HIV-infected men who have sex with men (MSM) have a higher prevalence of anal infection by high-risk HPV and incidence of anal carcinoma. Use of cART reduces the risk of acquiring anal infection by high-risk HPV.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Anamarija Pfeiffer, Giulia Franciosa, Marie Locard-Paulet, Ilaria Piga, Kristian Reckzeh, Vidyasiri Vemulapalli, Stephen C. Blacklow, Kim Theilgaard-Monch, Lars J. Jensen, Jesper V. Olsen
Summary: The protein tyrosine phosphatase SHP2 plays a crucial role in the oncogenic transformation of AML cells. By stabilizing SHP2 in its autoinhibited conformation, allosteric inhibitors show promise in inhibiting the RAS-ERK pathway and preventing cell proliferation and survival. Combination therapies that target SHP2 and other key enzymes can prevent the development of resistance.
Letter
Dermatology
A. Sernicola, P. Maddalena, I. La Greca, M. G. Dona, M. Salvi, V. Garelli, C. Stingone, L. Gianserra, E. Giuliani, M. Pontone, F. Pimpinelli, A. Latini
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Letter
Medicine, General & Internal
Maria Gabriella Don, Eugenia Giuliani, Mauro Zaccarelli, Alessandra Latini
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Oncology
Maria Benevolo, Alessandra Latini, Francesca Rollo, Massimo Giuliani, Amalia Giglio, Eugenia Giuliani, Antonio Cristaudo, Aldo Morrone, Maria Gabriella Dona
Summary: This study investigated the incidence of cytologic abnormalities in men who have sex with men (MSM) and found that there was no significant difference in the incidence between HIV-infected and uninfected individuals. However, the persistence of high-risk human papillomavirus (HPV), age, and condomless receptive anal sex were identified as predictors for abnormal cytology.
CANCER CYTOPATHOLOGY
(2023)
Article
Medicine, Research & Experimental
Daniel Oliveira, Kirsten G. Coupland, Wenchao Shao, Shaobo Jin, Francesca Del Gaudio, Sailan Wang, Rhys Fox, Julie W. Rutten, Johan Sandin, Henrik Zetterberg, Johan Lundkvist, Saskia Aj Lesnik Oberstein, Urban Lendahl, Helena Karlstrom
Summary: In this study, a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 extracellular domain (ECD) was developed and tested on CADASIL mice. The therapy successfully reduced NOTCH3 deposition around brain capillaries, increased microglia activation, and lowered serum levels of NOTCH3 ECD.
EMBO MOLECULAR MEDICINE
(2023)
Review
Immunology
Giulia Franciosa, Anders H. Kverneland, Agnete W. P. Jensen, Marco Donia, Jesper V. Olsen
Summary: Cancer survival relies on tumor cells evading immune recognition, but immunotherapy has shown promising results in metastatic cancers. Resistance mechanisms limit efficacy, so understanding the interplay between immune cells and tumors is crucial. Mass spectrometry-based proteomics may provide insights into tumor immunity and cancer immunotherapies, allowing for translational and clinical discoveries.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Review
Nutrition & Dietetics
Donatella Ambroselli, Fabrizio Masciulli, Enrico Romano, Giuseppina Catanzaro, Zein Mersini Besharat, Maria Chiara Massari, Elisabetta Ferretti, Silvia Migliaccio, Luana Izzo, Alberto Ritieni, Michela Grosso, Caterina Formichi, Francesco Dotta, Francesco Frigerio, Eleonora Barbiera, Anna Maria Giusti, Cinzia Ingallina, Luisa Mannina
Summary: The definition of metabolic syndrome (MetS) has changed over time due to the difficulty in establishing universal criteria. MetS is associated with a pro-inflammatory state related to altered glucose metabolism, leading to increased cardiovascular risk. Complications of MetS include cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Genetic factors, human microbiota, and diet play complex roles in the predisposition to MetS. This review summarizes the literature of the past decade on MetS, including its definition, pathophysiology, treatment approaches, prediction and diagnosis using advanced methodologies, and the role of specific foods in prevention and/or treatment.
Article
Cell Biology
V. Nieddu, V. Melocchi, C. Battistini, G. Franciosa, M. Lupia, C. Stellato, G. Bertalot, J. V. Olsen, N. Colombo, F. Bianchi, U. Cavallaro
Summary: Ovarian cancer (OC) has the highest mortality rate among gynecological tumors, primarily due to early peritoneal dissemination, tumor relapse, and chemoresistance. These events are initiated and sustained by ovarian cancer stem cells (OCSC) with self-renewing and tumor-initiating properties. Interfering with OCSC function could offer novel therapeutic perspectives.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Ana Martinez-Val, Kyle Fort, Claire Koenig, Leander van der Hoeven, Giulia Franciosa, Thomas Moehring, Yasushi Ishihama, Yu-ju Chen, Alexander Makarov, Yue Xuan, Jesper V. Olsen
Summary: This article presents a hybrid data-independent acquisition (DIA) strategy that combines targeted and discovery proteomics to achieve sufficient coverage of regulatory phosphorylation sites. By benchmarking against state-of-the-art targeted MS methods, the authors demonstrate the quantitative accuracy and sensitivity of hybrid-DIA and its ability to profile the global phosphoproteome. The robustness, sensitivity, and biomedical potential of hybrid-DIA are further demonstrated through profiling chemotherapeutic agents in single colon carcinoma multicellular spheroids and evaluating phospho-signaling differences in cancer cells.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Z. M. Besharat, S. Trocchianesi, A. Verrienti, R. Ciampi, S. Cantara, C. Romei, C. Sabato, T. M. R. Noviello, A. Po, A. Citarella, F. P. Caruso, I. Panariello, F. Gianno, G. Carpino, E. Gaudio, M. Chiacchiarini, L. Masuelli, M. Sponziello, V. Pecce, T. Ramone, F. Maino, F. Dotta, M. Ceccarelli, L. Pezzullo, C. Durante, M. G. Castagna, R. Elisei, E. Ferretti
Summary: The study aimed to identify non-invasive circulating biomarkers in medullary thyroid carcinoma (MTC). By analyzing tissue and plasma extracellular vesicle samples from MTC patients, a set of circulating miRNAs, including miR-26b-5p and miR-451a, were identified as diagnostic biomarkers. These miRNAs showed high expression levels and their expression decreased in disease-free patients during follow-up. The results provide a novel non-invasive tool for the molecular diagnosis of MTC.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Oncology
Giulia Diluvio, Tanya T. Kelley, Mohini Lahiry, Annamil Alvarez-Trotta, Ellen M. Kolb, Elena Shersher, Luisana Astudillo, Rhett A. Kovall, Stephan C. Schuerer, Anthony J. Capobianco
Summary: In this study, the first small-molecule inhibitor of NACK, Z271-0326, was discovered, which directly blocks Notch-mediated transcription and exhibits potent antineoplastic activity in PDX mouse models.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Oncology
Anna Citarella, Giuseppina Catanzaro, Zein Mersini Besharat, Sofia Trocchianesi, Federica Barbagallo, Giorgio Gosti, Marco Leonetti, Annamaria Di Fiore, Lucia Coppola, Tanja Milena Autilio, Zaira Spinello, Alessandra Vacca, Enrico De Smaele, Mary Anna Venneri, Elisabetta Ferretti, Laura Masuelli, Agnese Po
Summary: Colorectal cancer is a leading cause of cancer-related deaths, and chemoresistance is a major issue. The activation of Hedgehog-GLI and NOTCH signaling pathways plays a role in chemoresistance and the epithelial-to-mesenchymal transition (EMT) in colorectal cancer. In KRAS-mutated CRC, the inhibition of both the HH-GLI and NOTCH pathways is necessary to enhance chemosensitivity, while in BRAF-mutated CRC, the inhibition of HH-GLI alone is sufficient to promote chemosensitivity.
Review
Biochemistry & Molecular Biology
Valeria Lucarini, Daniela Nardozi, Valentina Angiolini, Monica Benvenuto, Chiara Focaccetti, Raffaele Carrano, Zein Mersini Besharat, Roberto Bei, Laura Masuelli
Summary: Gastrointestinal(GI) cancers are common and cause a significant number of cancer-related deaths. Metastasis is the primary cause of death from GI cancer, making it important to understand cancer cell migration and develop new therapies. This review summarizes the mechanisms of cancer cell migration and metastasis formation, focusing on the role of tumor microenvironment components. It also discusses the potential of microRNAs as biomarkers for prognosis, monitoring, and diagnosis in GI cancer patients. Additionally, the use of nutraceuticals as a strategy to target microRNAs and pathways involved in GI tumor invasiveness is explored.
Article
Medicine, Research & Experimental
Sofia Trocchianesi, Agnese Po, Anna Citarella, Zaira Spinello, Aurelia Rughetti, Zein Mersini Besharat, Tanja Milena Autilio, Valeria Pecce, Antonella Verrienti, Rossella Elisei, Cosimo Durante, Giuseppina Catanzaro, Elisabetta Ferretti
Summary: The aim of this study was to identify an escape mechanism in MTC cells exposed to a highly selective RET tyrosine-kinase inhibitor. The results showed that the inhibitor pralsetinib impaired MTC cell growth and induced cell death, and the Hedgehog-Gli (HH-Gli) pathway was identified as a new molecular mechanism of escape that can be overcome through combined therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)