Article
Pathology
Gulden Diniz, Berna Komurcuoglu, Berk Ozyilmaz, Alp Ozguzer, Nur Yucel, Ozgur Kirbiyik
Summary: The study aimed to investigate the prevalence of ALK, ROS1, and EGFR genetic variations in lung cancer patients, with findings showing higher rates of ALK rearrangements in young and female patients, and more EGFR mutations, especially exon 19 deletions, in females. Despite the lower-than-expected frequency of molecular changes, suggesting the influence of smoking habits, no statistical significance was found in the association between EGFR alterations and gender or age.
INDIAN JOURNAL OF PATHOLOGY AND MICROBIOLOGY
(2022)
Review
Oncology
Mercedes Herrera-Juarez, Cristina Serrano-Gomez, Helena Bote-de-Cabo, Luis Paz-Ares
Summary: Precision oncology aims to design the best cancer treatment based on tumor biology. In NSCLC, patients with actionable genomic aberrations can benefit from targeted therapy, such as EGFR mutations and ALK rearrangements. Effective inhibitors have been developed for various druggable targets, leading to a paradigm shift in NSCLC treatment.
Article
Multidisciplinary Sciences
Xiaolin Ji, Yan Liu, Fang Mei, Xinyang Li, Mengxue Zhang, Buwen Yao, Rui Wu, Jiangfeng You, Fei Pei
Summary: This study investigated the prevalence of ALK fusion in Chinese lung cancer patients and found that ALK-positive patients without targeted therapy had poor outcomes, suggesting that the PI3K/AKT/SPP1 pathway may be a promising target for aggressive lung cancer patients.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Ines Mota, Enrico Patrucco, Cristina Mastini, Navin R. Mahadevan, Tran C. Thai, Elisa Bergaggio, Taek-Chin Cheong, Giulia Leonardi, Elif Karaca-Atabay, Marco Campisi, Teresa Poggio, Matteo Menotti, Chiara Ambrogio, Dario L. Longo, Susan Klaeger, Hasmik Keshishian, Zsofia M. Sztupinszki, Zoltan Szallasi, Derin B. Keskin, Jonathan S. Duke-Cohan, Bruce Reinhold, Steven A. Carr, Catherine J. Wu, Kelly D. Moynihan, Darrell J. Irvine, David A. Barbie, Ellis L. Reinherz, Claudia Voena, Mark M. Awad, Rafael B. Blasco, Roberto Chiarle
Summary: Mota et al. demonstrate that immunogenic ALK peptides can enhance the response to immune checkpoint blockade in ALK-rearranged NSCLC mouse models. They also identify immunogenic human ALK peptides for future translational research.
Article
Multidisciplinary Sciences
Xiaoyu Han, Jun Fan, Yumin Li, Yukun Cao, Jin Gu, Xi Jia, Yuhui Wang, Heshui Shi
Summary: This study aimed to identify the relationships of EGFR mutations and ALK status with CT characteristics in adenocarcinoma using a large patient cohort. The most significant independent prognostic factors of EGFR effective mutations were female sex, nonsmoker status, GGO air bronchograms, and pleural retraction. The use of CT features in combination with clinical variables showed superiority in predicting ALK positivity compared to using clinical variables alone.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Michelle Wang, Shadera Slatter, Jesse Sussell, Chia-Wei Lin, Sarika Ogale, Debajyoti Datta, Atul J. Butte, Lyudmila Bazhenova, Vivek A. Rudrapatna
Summary: This study aimed to evaluate the treatment patterns, safety, and effectiveness outcomes of ALK tyrosine kinase inhibitors (TKIs) in real-world patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC). The results showed that ALK TKIs were well tolerated and alectinib was associated with longer time to adverse events, disease progression, and death. Proactive monitoring for adverse events such as rash, bradycardia, and hepatotoxicity may help optimize the use of ALK TKIs in this patient population.
Article
Oncology
Angela Bellini, Ulrike Poetschger, Virginie Bernard, Eve Lapouble, Sylvain Baulande, Peter F. Ambros, Nathalie Auger, Klaus Beiske, Marie Bernkopf, David R. Betts, Jaydutt Bhalshankar, Nick Bown, Katleen de Preter, Nathalie Clement, Valerie Combaret, Jaime Font de Mora, Sally L. George, Irene Jimenez, Marta Jeison, Barbara Marques, Tommy Martinsson, Katia Mazzocco, Martina Morini, Annick Muehlethaler-Mottet, Rosa Noguera, Gaelle Pierron, Maria Rossing, Sabine Taschner-Mandl, Nadine Van Roy, Ales Vicha, Louis Chesler, Walentyna Balwierz, Victoria Castel, Martin Elliott, Per Kogner, Genevieve Laureys, Roberto Luksch, Josef Malis, Maja Popovic-Beck, Shifra Ash, Olivier Delattre, Dominique Valteau-Couanet, Deborah A. Tweddle, Ruth Ladenstein, Gudrun Schleiermacher
Summary: Genetic alterations of ALK (clonal mutations and amplifications) in high-risk neuroblastoma patients are independent predictors of poorer survival. These data provide a rationale for the integration of ALK inhibitors in upfront treatment of high-risk neuroblastoma with ALK alterations.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Carolina Rosswog, Jana Fassunke, Angela Ernst, Birgid Schoemig-Markiefka, Sabine Merkelbach-Bruse, Christoph Bartenhagen, Maria Cartolano, Sandra Ackermann, Jessica Theissen, Mirjam Blattner-Johnson, Barbara Jones, Kathrin Schramm, Janine Altmueller, Peter Nuernberg, Monika Ortmann, Frank Berthold, Martin Peifer, Reinhard Buettner, Frank Westermann, Johannes H. Schulte, Thorsten Simon, Barbara Hero, Matthias Fischer
Summary: Genomic alterations of the ALK gene occur recurrently in neuroblastoma, with ALK mutations occurring in 10.5% of cases at diagnosis and increasing by 70% at relapse. However, the frequency of ALK amplifications does not change over the course of the disease. Regular monitoring of the genomic ALK status and evaluation of ALK-targeted treatment in intermediate-risk patients is recommended.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Gang Xiao, Lifeng Li, Guilong Tanzhu, Zhiyuan Liu, Xuan Gao, Xin Wan, Desheng Xiao, Liu Chen, Xuefeng Xia, Rongrong Zhou
Summary: This study found that lung adenocarcinomas (LUAD) with EGFR-positive and ALK-positive had a suppressive tumor immune microenvironment (TIME) and were less responsive to immunotherapy. The TIME in patients with EGFR/ALK-positive LUAD brain metastases (BMs) was different from that in primary lung cancer. Evaluating the immune characteristics of LUAD BMs is important for clinical treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Dilara Akhoundova, Martina Haberecker, Ralph Fritsch, Sylvia Hoeller, Michael K. Kiessling, Markus Rechsteiner, Jan H. Rueschoff, Alessandra Curioni-Fontecedro
Summary: This study explores the clinical impact of identifying ALK rearrangement in LCNEC patients and highlights the importance of comprehensive molecular profiling in order to detect actionable genomic alterations.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Haoyue Hu, Songtao Tan, Meng Xie, Peng Guo, Qiang Yu, Juan Xiao, Kangrui Zhao, Qiong Liao, Yi Wang
Summary: In non-small cell lung cancer, concurrent genetic alterations of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are rare, but their clinical and pathological characteristics are not well-defined, and the optimal treatment approach remains controversial. This report presents a case of stage IV lung adenocarcinoma with both EGFR and ALK mutations, along with high PD-L1 expression. The patient initially received treatment with EGFR tyrosine kinase inhibitors (TKIs), but the disease progressed, and regression was achieved following a switch to ALK-TKI therapy and local radiotherapy. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for NSCLC patients with concurrent EGFR mutation and ALK rearrangement.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Evgeny N. Imyanitov, Aglaya G. Iyevleva, Evgeny V. Levchenko
Summary: Molecular testing is essential in NSCLC management, including detecting mutations and translocations, as well as analyzing protein expression. Efforts are ongoing to integrate multiple molecular assays into a single diagnostic pipeline for NSCLC.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Oncology
Elizabeth R. Tucker, Irene Jimenez, Lindi Chen, Angela Bellini, Chiara Gorrini, Elizabeth Calton, Qiong Gao, Harvey Che, Evon Poon, Yann Jamin, Barbara Martins Da Costa, Karen Barker, Sumana Shrestha, J. Ciaran Hutchinson, Simran Dhariwal, Angharad Goodman, Elaine Del Nery, Pierre Gestraud, Jaydutt Bhalshankar, Yasmine Iddir, Elnaz Saberi-Ansari, Alexandra Saint-Charles, Birgit Geoerger, Maria Eugenia Marques Da Costa, Cecile Pierre-Eugene, Isabelle Janoueix-Lerosey, Didier Decaudin, Fariba Nemati, Angel M. Carcaboso, Didier Surdez, Olivier Delattre, Sally L. George, Louis Chesler, Deborah A. Tweddle, Gudrun Schleiermacher
Summary: ALK-activating mutations are present in approximately 10% of neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation ALK inhibitor, is being considered as a treatment for children with ALK-aberrant neuroblastoma. Resistance to single-agent treatment has been reported, and combination therapies with chemotherapy or MDM2 inhibitor are being explored to improve treatment efficacy.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Yaping Zhang, Hui Wang, Xiaoyan Wang, Shuai Li, Hongming Fang
Summary: EGFR, ALK, and ROS1 mutations are typically considered mutually exclusive. This article describes a rare case of a patient with triple mutations in EGFR, ALK, and ROS1 in advanced NSCLC, who responded well to multiple treatment options with a slightly poorer overall survival than patients with single driver gene mutations.
CLINICAL LUNG CANCER
(2021)
Article
Oncology
Yuki Katayama, Tadaaki Yamada, Keiko Tanimura, Shinsaku Tokuda, Kenji Morimoto, Soichi Hirai, Yohei Matsui, Ryota Nakamura, Masaki Ishida, Hayato Kawachi, Kazue Yoneda, Kazutaka Hosoya, Takahiro Tsuji, Hiroaki Ozasa, Akihiro Yoshimura, Masahiro Iwasaku, Young Hak Kim, Mano Horinaka, Toshiyuki Sakai, Takahiro Utsumi, Shinsuke Shiotsu, Takayuki Takeda, Ryohei Katayama, Koichi Takayama
Summary: In this study, it was found that epidermal growth factor receptor (EGFR) signaling is involved in adaptive resistance to lorlatinib in ALK-rearranged NSCLC. EGFR inhibition enhanced ALK inhibition-induced apoptosis and halted the proliferation of ALK-rearranged lung cancer cells. Combination therapy with EGFR inhibitor and lorlatinib significantly suppressed tumor regrowth after cessation of treatment. This study provides new insights into tumor evolution and the development of combined therapeutic strategies for ALK-rearranged lung cancer.
NPJ PRECISION ONCOLOGY
(2023)
Review
Cell Biology
Sara E. Monaco, Luka Brcic, Sanja Dacic
Summary: This article provides a timely update on the challenges of diagnosing mesothelial proliferations, specifically mesotheliomas, in body cavity cytology samples. While immunohistochemical and fluorescence in situ hybridization studies can assist in determining mesothelial origin and distinguishing malignant proliferations from benign ones, caution is advised due to important pitfalls when interpreting these cases.
Article
Medical Laboratory Technology
Luka Brcic, Nolwenn Le Stang, Florian Gallob, Daniel Pissaloux, Ruth Sequeiros, Sandrine Paindavoine, Jean Claude Pairon, Marie Karanian, Sanja Dacic, Nicolas Girard, Andrew Churg, Franck Tirode, Francoise Galateau-Salle
Summary: Immunohistochemistry for MTAP and p16 can serve as a surrogate for CDKN2A HD in pleural mesotheliomas. Loss of nuclear p16 (<1% staining) and cytoplasmic MTAP (<=30% staining) indicates poor prognosis in pleural mesothelioma patients.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2023)
Article
Oncology
Suyang Li, Guihuan Qiu, Jun Wu, Jiaxin Ying, Haiyi Deng, Xiaohong Xie, Xinqing Lin, Zhanhong Xie, Yinyin Qin, Yansheng Wang, Xiaodong Ma, Luka Brcic, Mariano Provencio, Yangchao Chen, Chengzhi Zhou, Ming Liu
Summary: Ferroptosis-related genes can serve as prognostic markers for small cell lung cancer (SCLC) patients and are associated with tumor immune infiltration. The expression of TXNIP is highly correlated with immune infiltration and the efficacy of chemotherapy combined with immunotherapy in SCLC patients.
TRANSLATIONAL LUNG CANCER RESEARCH
(2022)
Article
Oncology
Philipp Jurmeister, Maximilian Leitheiser, Peggy Wolkenstein, Frederick Klauschen, David Capper, Luka Brcic
Summary: The combination of DNA methylation analysis and machine learning can reliably differentiate pleural mesothelioma (PM) from chronic pleuritis and lung cancer, including pleomorphic carcinomas. Additionally, the study identifies new candidate genes for PM carcinogenesis and demonstrates that deconvolution of DNA methylation data can provide insights into the composition of the tumor microenvironment.
Article
Pathology
Jan Hendrik Rueschoff, Martina Haberecker, Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini, Joachim G. Aerts, Emanuela Felley-Bosco, Michaela B. Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P. Finn, Enrico Silini, Jan von der Thusen, Nesa Marti, Karerina Vervita, Roswitha Kammler, Solange Peters, Rolf A. Stahel, Paul Baas, Isabelle Opitz
Summary: Pleural mesothelioma (PM) is a aggressive malignancy with poor prognosis. Low phosphorylated S6 (pS6) immunoreactivity is significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. In this study, high pS6 expression is associated with lower likelihood of complete resection and shorter OS and PFS in non-epithelioid PM patients.
Correction
Pathology
Jan Hendrik Ruschoff, Martina Haberecker, Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini, Joachim G. Aerts, Emanuela Felley-Bosco, Michaela B. Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P. Finn, Enrico Silini, Jan von der Thusen, Nesa Marti, Karerina Vervita, Roswitha Kammler, Solange Peters, Rolf A. Stahel, Paul Baas, Isabelle Opitz
Letter
Oncology
Markus G. Seidel, Luka Brcic, Gerald Hoefler, Caroline Hutter, Milen Minkov, Laura Sophie Steffen, Armin Zebisch, Martin Benesch
PEDIATRIC BLOOD & CANCER
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Birgit Pernthaler, Luka Brcic, Reingard Maria Aigner, Michael Fuchsjaeger, Emina Talakic
Summary: This article presents a rare case of primary malignant mesothelioma in the liver, with the patient being a 48-year-old woman who experienced increasing upper abdominal discomfort and inappetence, accompanied by a weight loss of approximately 10 kg. CT and MRI revealed a highly suspicious mass lesion in the liver. F-18-FDG PET/CT performed for staging showed a pathological F-18-FDG uptake of the known liver tumor. Histology and immunohistochemistry indicated mesothelioma of the liver.
CLINICAL NUCLEAR MEDICINE
(2023)
Article
Oncology
Abbas Agaimy, Luka Brcic, Laurence M. Briski, Yin P. Hung, Michael Michal, Michal Michal, G. Petur Nielsen, Robert Stoehr, Andrew E. Rosenberg
Summary: A focal adenomatoid-microcystic pattern is not uncommon in peritoneal mesothelioma, but tumors composed almost exclusively of this pattern are distinctly rare and have not been well characterized. Herein, we describe five peritoneal mesothelial neoplasms that are pure adenomatoid/microcystic in morphology and unified by the presence of an NR4A3 fusion. These tumors showed morphological similarities and lacked a conventional epithelioid or sarcomatoid component. At the last follow-up, all five patients were alive and disease-free.
GENES CHROMOSOMES & CANCER
(2023)
Article
Cell Biology
Stephan Ihrler, David Stiefel, Philipp Jurmeister, Ann Sandison, Nicola Chaston, Jan Laco, Nina Zidar, Luka Brcic, Robert Stoehr, Abbas Agaimy
Summary: The formal pathogenesis of salivary carcinosarcoma (SCS) is clarified in this study, showing that it almost always develops from pleomorphic adenoma (PA) and follows a multistep adenoma-carcinoma-sarcoma sequence. This finding suggests that SCS is a rare and unique variant of carcinoma ex PA with secondary sarcomatous overgrowth.
Article
Immunology
Arailym Sarsembayeva, Melanie Kienzl, Eva Gruden, Dusica Ristic, Kathrin Maitz, Paulina Valadez-Cosmes, Ana Santiso, Carina Hasenoehrl, Luka Brcic, Joerg Lindenmann, Julia Kargl, Rudolf Schicho
Summary: Cannabinoid (CB) receptors, particularly CB2, play an important role in the tumor microenvironment of non-small cell lung cancer (NSCLC). Deficiency of CB2 reduces tumor burden and enhances the activity of immune cells, leading to improved response to anti-PD-1 therapy. CB2 could be a potential adjuvant target for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sabrina Borchert, Alexander Mathilakathu, Alina Nath, Michael Wessolly, Elena Mairinger, Daniel Kreidt, Julia Steinborn, Robert F. H. Walter, Daniel C. Christoph, Jens Kollmeier, Jeremias Wohlschlaeger, Thomas Mairinger, Luka Brcic, Fabian D. Mairinger
Summary: The expression level of Fibroblast activation protein alpha (FAP) is associated with the formation of desmoplastic stromal reaction (DSR) in pleural mesothelioma (PM). DSR-high samples demonstrated a significant prolongation of median survival time, indicating the important role of cancer-associated fibroblasts (CAFs) in tumor prognosis. These findings provide a basis for introducing new therapeutic strategies and predictive biomarkers for survival in PM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Tanja Grossmann, Andrijana Kirsch, Magdalena Grill, Barbara Steffan, Michael Karbiener, Luka Brcic, Barbara Darnhofer, Ruth Birner-Gruenberger, Markus Gugatschka
Summary: Research on human vocal fold biology is limited due to the sensitive microstructure of the vocal fold mucosa. We developed an alternative model using human buccal epithelial cells and vocal fold fibroblasts, which closely resembles native vocal fold mucosa in terms of histology and proteomics. This model provides a reproducible in vitro platform for various research opportunities.
Article
Respiratory System
Teresa Sassmann, Philipp Douschan, Vasile Foris, Natascha Troester, Katarina Zeder, Luka Brcic, Adrienn Tornyos, Gerhard Bachmaier, Michael Fuchsjaeger, Horst Olschewski, Gabor Kovacs
Summary: Even in the absence of significant pulmonary hypertension at rest, COPD patients show characteristic abnormalities in pulmonary hemodynamics during exercise, which may impact exercise capacity.
RESPIRATORY RESEARCH
(2022)
Correction
Pathology
Jan Hendrik Ruschoff, Martina Haberecker, Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini, Joachim G. Aerts, Emanuela Felley-Bosco, Michaela B. Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P. Finn, Enrico Silini, Jan von der Thusen, Nesa Marti, Karerina Vervita, Roswitha Kammler, Solange Peters, Rolf A. Stahel, Paul Baas, Isabelle Opitz