Article
Biochemistry & Molecular Biology
Mitsuteru Hiwatari, Masafumi Seki, Ryosuke Matsuno, Kenichi Yoshida, Takeshi Nagasawa, Aiko Sato-Otsubo, Shohei Yamamoto, Motohiro Kato, Kentaro Watanabe, Masahiro Sekiguchi, Satoru Miyano, Seishi Ogawa, Junko Takita
Summary: A fusion gene composed of portions of the TENM3 gene and the ALK gene has been identified in tumor cells from patients with neuroblastoma. The fusion gene leads to the formation of a fusion protein with constitutive tyrosine kinase activity, which may serve as a therapeutic target and diagnostic molecular marker for neuroblastoma.
Article
Oncology
Gavin D. Garland, Stephen P. Ducray, Leila Jahangiri, Perla Pucci, G. A. Amos Burke, Jack Monahan, Raymond Lai, Olaf Merkel, Ana-Iris Schiefer, Lukas Kenner, Andrew J. Bannister, Suzanne D. Turner
Summary: Research has shown that nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) drives anaplastic large cell lymphoma (ALCL) by regulating another protein, BRG1, to promote tumor cell proliferation. Inactivation of the gene that leads to expression of BRG1 results in tumor cell death, suggesting that therapeutic targeting of BRG1 may be a novel therapy for this form of cancer.
Article
Oncology
Josephina Sampson, Hyun-min Ju, Ji-young Song, Andrew M. Fry, Richard Bayliss, Jene Choi
Summary: The study evaluated the potential of combination chemotherapy using vincristine and potent ALK drugs. It was found that cells carrying the EML4-ALK V3 mutation exhibited low response to the drug combination due to high levels of tubulin acetylation and active proliferation pathways.
Review
Chemistry, Medicinal
Mei Elsayed, Petros Christopoulos
Summary: ALK(+) NSCLC is a model disease for targeted pharmaceuticals, with second-generation ALK TKIs replacing crizotinib as standard first-line treatment. Tissue or liquid rebiopsies are important for individualized patient management, especially for cases with off-target resistance.
Article
Oncology
Yuki Uchihara, Kenji Tago, Hiroomi Tamura, Megumi Funakoshi-Tago
Summary: NPM-ALK localizes to the nucleolus by binding to NPM1 and interacts with EBP2, inducing tyrosine phosphorylation. Knockdown of EBP2 activates p53 via the Akt-mTORC1 pathway in NPM-ALK-positive cells, providing a potential therapeutic target for ALCL treatment.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Loelia Babin, Alice Darchen, Elie Robert, Zakia Aid, Rosalie Borry, Claire Soudais, Marion Piganeau, Anne De Cian, Carine Giovannangeli, Olivia Bawa, Charlotte Rigaud, Jean-Yves Scoazec, Lucile Couronne, Layla Veleanu, Agata Cieslak, Vahid Asnafi, David Sibon, Laurence Lamant, Fabienne Meggetto, Thomas Mercher, Erika Brunet
Summary: This study generated a model of ALK+ ALCL lymphomagenesis by editing the NPM-ALK fusion gene in mature T lymphocytes, and identified the activation of the WNT signaling pathway and the expression of ROR2 as potential therapeutic targets for ALK+ ALCL.
Letter
Oncology
Daniel Weber, Miriam Decker, Michael Schuster, Sara Folz, Carsten Johannes Sturmer, Manfred P. Lutz
Summary: Aseptic abscesses under treatment with Crizotinib are not limited to the kidneys but can also occur in other abdominal organs and even in the thoracic wall, suggesting a yet unknown tissue-independent mechanism of action.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Yue Lu, Zhenzhen Fan, Su-Jie Zhu, Xiaoxing Huang, Zhongji Zhuang, Yunzhan Li, Zhou Deng, Lei Gao, Xuehui Hong, Ting Zhang, Li Li, Xihuan Sun, Wei Huang, Jingfang Zhang, Yan Liu, Baoding Zhang, Jie Jiang, Fu Gui, Zheng Wang, Qiyuan Li, Siyang Song, Xin Huang, Qiao Wu, Lanfen Chen, Dawang Zhou, Jianming Zhang, Cai-Hong Yun, Liang Chen, Xianming Deng
Summary: XMU-MP-5 is a new-generation ALK inhibitor developed to overcome crizotinib resistance mutations, showing promising efficacy in preclinical studies against clinically relevant secondary ALK mutations.
EMBO MOLECULAR MEDICINE
(2022)
Article
Oncology
Estela Sanchez-Herrero, Roberto Serna-Blasco, Vadym Ivanchuk, Rosario Garcia-Campelo, Manuel Domine Gomez, Jose M. Sanchez, Bartomeu Massuti, Noemi Reguart, Carlos Camps, Sandra Sanz-Moreno, Silvia Calabuig-Farinas, Eloisa Jantus-Lewintre, Magdalena Arnal, Dietmar Fernandez-Orth, Virginia Calvo, Victor Gonzalez-Rumayor, Mariano Provencio, Atocha Romero
Summary: Despite durable responses, NSCLC patients treated with ALK inhibitors eventually develop resistance. Liquid biopsy NGS analysis upon disease progression identified diverse potential ALK-I-resistance mutations and may be a valuable tool for therapy decision-making.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Farzaneh Aboualizadeh, Zhong Yao, Jikui Guan, Luka Drecun, Shivanthy Pathmanathan, Jamie Snider, Ganesh Umapathy, Max Kotlyar, Igor Jurisica, Ruth Palmer, Igor Stagljar
Summary: This study systematically characterized the phospho-dependent ALK interactome using the MaMTH system, identifying 30 novel ALK interactors from a library of 86 SH2 domain-containing full length proteins. The interactions of these novel proteins are correlated to ALK phosphorylation activity and NCK2 was further validated as a key interactor in neuroblastoma cells. The study provides a valuable resource list of potential novel ALK signaling components for further exploration.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Jiwei Shen, Yuting Meng, Kunlun Wang, Minghuan Gao, Jianan Du, Junfang Wang, Zengqiang Li, Daiying Zuo, Yingliang Wu
Summary: The EML4-ALK G1202R mutation mediates epithelial-mesenchymal transition and resistance to ceritinib in NSCLC by activating the STAT3/Slug signaling pathway. Combination therapy with STAT3 and ALK inhibitors may overcome this drug resistance.
CELLULAR SIGNALLING
(2022)
Review
Oncology
Yuan Wang, Jing He, Manyu Xu, Qingfeng Xue, Cindy Zhu, Juan Liu, Yaping Zhang, Wenyu Shi
Summary: This review provides an overview of research progress on ALK+ ALCL, including the study of drug resistance mechanisms and the application and development of new therapies. Potential treatment strategies are proposed to guide the design of future clinical trials.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Dimitrios Chioureas, Janina Beck, George Baltatzis, Ioulia Vardaki, Pedro Fonseca, Nikolaos Tsesmetzis, Francisco Vega, Vasiliki Leventaki, Aristides G. Eliopoulos, Elias Drakos, George Z. Rassidakis, Theocharis Panaretakis
Summary: ALK+ anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma characterized by overexpression and activation of ALK kinase due to chromosomal translocations. This study demonstrates that ALK+ ALCL cells secrete exosomes containing critical components of ALK signaling which can be taken up by other cells, influencing tumor microenvironment and possibly contributing to treatment resistance. The interactions between ALK signaling and the microenvironment in ALK+ ALCL are not fully understood, but this research shows that exosome-mediated activation of stromal cells can alter the cytokine profile of the microenvironment, potentially impacting tumor aggressiveness and resistance to treatment.
Article
Oncology
Shilan Liu, Xiao Liu, Ting Wang, Chunhua Zeng, Baichen Ren, Xiaodan Yu, Min Xu, Wenjuan Li, Zhihui Qiao, Chuanyun You, Qinghui Yang, Mei Chen
Summary: Choroidal metastasis as an initial presenting feature of lung cancer with EML4-ALK translocation is rare and lacks effective treatment. This case study presents a 57-year-old woman with choroidal metastases secondary to lung cancer and EML4-ALK translocation, who achieved a rapid and complete response to oral administration of crizotinib without local treatment or systemic chemotherapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
A. A. Bokhari, W-Y Lai, A. T. Le, J. L. Gabre, T-P Chuang, S. Fransson, B. Bergman, A. Djos, N. Chen, T. Martinsson, J. Van den Eynden, R. C. Doebele, R. H. Palmer, B. Hallberg, G. Umapathy
Summary: This study developed four novel EML4-ALK-positive NSCLC cell lines and characterized them through RNA sequencing and whole-genome sequencing. These cell lines showed differential sensitivity to ALK tyrosine kinase inhibitors, and the ribonucleotide reductase regulatory subunit 2 (RRM2) was identified as a potential therapeutic target in ALK-positive NSCLC.
Article
Biochemistry & Molecular Biology
Liesa S. Ziegler, Marlene C. Gerner, Ralf L. J. Schmidt, Doris Trapin, Peter Steinberger, Winfried F. Pickl, Christian Sillaber, Gerda Egger, Ilse Schwarzinger, Klaus G. Schmetterer
Summary: Recent studies have shown that FOXP3 in human Treg negatively regulates the NF-kappa B signaling pathway, and the activation and suppressive capacity of Treg are not dependent on this pathway.
Article
Biochemistry & Molecular Biology
Thomas Dillinger, Raheleh Sheibani-Tezerji, Walter Pulverer, Ines Stelzer, Melanie R. Hassler, Janine Scheibelreiter, Carlos Uziel Perez Malla, Madeleine Kuroll, Sandra Domazet, Elisa Redl, Sarah Ely, Stefanie Brezina, Andreas Tiefenbacher, Katharina Rebhan, Nicolai Hubner, Bernhard Grubmueller, Markus Mitterhauser, Marcus Hacker, Andreas Weinhaeusel, Judit Simon, Markus Zeitlinger, Andrea Gsur, Gero Kramer, Shahrokh F. Shariat, Lukas Kenner, Gerda Egger
Article
Medicine, Legal
Wim H. De Jong, Demosthenes Panagiotakos, Ana Proykova, Theodoros Samaras, Mark W. Clemens, Daphne De Jong, Ingrid Hopper, Hinne A. Rakhorst, Fabio Santanelli di Pompeo, Suzanne D. Turner
Summary: The SCHEER was requested to provide a scientific opinion on the safety of breast implants in relation to ALCL by the EC. Different surface textures of breast implants may present different risks, but the causality between textured breast implants and BIA-ALCL is considered moderate. New cases reported by national clinical registries are crucial for estimating the risk of BIA-ALCL.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Cell Biology
Rachel Ulferts, Elena Marcassa, Lewis Timimi, Liam Changwoo Lee, Andrew Daley, Beatriz Montaner, Suzanne Dawn Turner, Oliver Florey, John Kenneth Baillie, Rupert Beale
Summary: Aside from its common association with autophagosomes, LC3 can be recruited to membranes through covalent lipidation in various non-canonical contexts, such as responses to ionophores. Different factors, including the RALGAP complex for M2-induced LC3 lipidation, ATG4D for LC3 recycling, and a vacuolar ATPase subunit for non-canonical LC3 recruitment, may play roles in lipidation processes in different environments. Influenza-induced and ionophore drug-induced LC3 lipidation can result in the association of vacuolar ATPase and ATG16L1, which can be inhibited by Salmonella SopF, suggesting a potential response to damage by various invasive pathogens.
Article
Oncology
Gavin D. Garland, Stephen P. Ducray, Leila Jahangiri, Perla Pucci, G. A. Amos Burke, Jack Monahan, Raymond Lai, Olaf Merkel, Ana-Iris Schiefer, Lukas Kenner, Andrew J. Bannister, Suzanne D. Turner
Summary: Research has shown that nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) drives anaplastic large cell lymphoma (ALCL) by regulating another protein, BRG1, to promote tumor cell proliferation. Inactivation of the gene that leads to expression of BRG1 results in tumor cell death, suggesting that therapeutic targeting of BRG1 may be a novel therapy for this form of cancer.
Review
Oncology
Lucy Hare, G. A. Amos Burke, Suzanne D. Turner
Summary: Overall, non-Hodgkin lymphoma (NHL) diagnosed in children, especially anaplastic large cell lymphoma (ALCL), has good survival outcomes with multi-agent chemotherapy. However, treatment side effects are common and relapse rates are high. Targeted therapies are seen as potential solutions, but the development of resistance remains a major challenge that requires further research to address.
Article
Chemistry, Medicinal
Theresa Balber, Loan Tran, Katarina Bencurova, Julia Raitanen, Gerda Egger, Markus Mitterhauser
Summary: Personalized treatment of cancer requires specific and validated biomarkers for tumor diagnosis and therapy. Translational preclinical models that accurately recapitulate human diseases are needed for the development and validation of these biomarkers, and there is a need for collaboration and knowledge sharing among different disciplines.
Article
Biochemistry & Molecular Biology
Tanja Limberger, Michaela Schlederer, Karolina Trachtova, Ines Garces de los Fayos Alonso, Jiaye Yang, Sandra Hoegler, Christina Sternberg, Vojtech Bystry, Jan Oppelt, Boris Tichy, Margit Schmeidl, Petra Kodajova, Anton Jaeger, Heidi A. Neubauer, Monika Oberhuber, Belinda S. Schmalzbauer, Sarka Pospisilova, Helmut Dolznig, Wolfgang Wadsak, Zoran Culig, Suzanne D. Turner, Gerda Egger, Sabine Lagger, Lukas Kenner
Summary: This study reveals the functional consequences of truncation mutations of the KMT2C gene in prostate cancer, showing that these mutations drive proliferation and formation of PIN. Loss of both KMT2C and PTEN in prostate cancer leads to loss of senescence, metastatic dissemination, and reduced life expectancy. The study highlights the prognostic significance of KMT2C mutation status and suggests MYC signalling axis inhibition as a potential treatment option for patients with KMT2C truncations and poor prognosis.
Article
Cell Biology
Masa Zrimsek, Hana Kucharikova, Kristina Draganic, Pavlina Dobrovolna, Verena Heiss Spornberger, Lisa Winkelmayer, Melanie R. Hassler, Gabriela Lochmanova, Zbynek Zdrahal, Gerda Egger
Summary: Histone deacetylases (HDACs) play important roles in regulating genomic stability, cell cycle, cell death, and differentiation, particularly in tumorigenesis. This study investigated the effects of HDAC inhibition in tumor cells using drug treatment and gene deletion approaches. Changes in protein expression and acetylation were measured, revealing alterations in overall protein abundance and increased acetylation of histones and non-histone proteins, with potential implications for metabolic and DNA damage pathways.
Article
Radiology, Nuclear Medicine & Medical Imaging
Valentin al Jalali, Gabriel Wasinger, Sazan Rasul, Bernhard Grubmueller, Beatrix Wulkersdorfer, Theresa Balber, Markus Mitterhauser, Judit Simon, Marcus Hacker, Shahrokh Shariat, Gerda Egger, Markus Zeitlinger
Summary: The present study investigated the potential use of PET imaging as a substitute for immunohistochemical analysis of tumor samples in prostate cancer patients. The correlation between imaging signals of two PET tracers and target structures was assessed. The findings suggest that [18F]FDHT PET may be useful for monitoring AR expression and alterations in AR expression during treatment.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Editorial Material
Surgery
Suzanne D. Turner
AESTHETIC SURGERY JOURNAL
(2023)
Article
Oncology
Katarina Bencurova, Joachim Friske, Maximilian Anderla, Manuela Mayrhofer, Thomas Wanek, Lukas Nics, Gerda Egger, Thomas H. Helbich, Marcus Hacker, Alexander Haug, Markus Mitterhauser, Theresa Balber
Summary: This study evaluated the potential of the radiotracer [Ga-68]Ga-Pentixafor in colorectal cancer (CRC) imaging using a CAM-xenograft model. The results showed specific accumulation of [Ga-68]Ga-Pentixafor in CAM-xenografts derived from HT29 cells, indicating its potential as a novel radiotracer for CRC imaging. The study also demonstrated the suitability of the CAM-xenograft model for preclinical evaluation of targeted radiopharmaceuticals.
Article
Gastroenterology & Hepatology
Velina S. Atanasova, Crhistian de Jesus Cardona, Vaclav Hejret, Andreas Tiefenbacher, Theresia Mair, Loan Tran, Janette Pfneissl, Kristina Draganic, Carina Binder, Julijan Kabiljo, Janik Clement, Katharina Woeran, Barbara Neudert, Sabrina Wohlhaupter, Astrid Haase, Sandra Domazet, Markus Hengstschlaeger, Markus Mitterhauser, Leonhard Muellauer, Boris Tichy, Michael Bergmann, Gabriele Schweikert, Markus Hartl, Helmut Dolznig, Gerda Egger
Summary: Researchers developed a colorectal cancer organoid model that incorporates both epithelial tumor cells and stromal fibroblasts, providing a more accurate representation of the tumor microenvironment. This model can be used to study disease mechanisms and therapy response in colorectal cancer.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Surgery
Emily R. James, Roberto N. Miranda, Suzanne D. Turner
Summary: Breast lymphomas are rare tumors originating from the lymphoid tissue of the breast and consist of neoplastic B or T cells. This article discusses the clinical presentations, histological and immunohistochemical features, and treatment options for breast lymphoma, emphasizing the importance of timely and accurate diagnosis.
