Review
Oncology
Cheng-Hao Chuang, Hsiao-Ling Chen, Hsiu-Mei Chang, Yu-Chen Tsai, Kuan-Li Wu, I-Hua Chen, Kung-Chao Chen, Jui-Ying Lee, Yong-Chieh Chang, Chin-Ling Chen, Yu-Kang Tu, Jen-Yu Hung, Chih-Jen Yang, Inn-Wen Chong
Summary: Anaplastic lymphoma kinase inhibitors have shown excellent efficacy in treating non-small cell lung cancer patients, with lorlatinib and low-dose alectinib performing well in first-line treatment. Different agents have varying advantages in terms of outcomes, highlighting the need for further large-scale phase III clinical trials to confirm conclusions.
Article
Multidisciplinary Sciences
Yoko Ota, Hiroyuki Yoda, Takahiro Inoue, Takayoshi Watanabe, Yoshinao Shinozaki, Atsushi Takatori, Hiroki Nagase
Summary: The study demonstrates the inhibitory effects of the newly developed ALK inhibitor CCC-003 on cell proliferation in ALK-mutated neuroblastoma, suggesting its potential for treating neuroblastoma and overcoming tyrosine kinase inhibitor resistance. CCC-003 preferentially binds to mutated DNA within the ALK gene and exerts anti-tumor activity through a distinct mode of action compared to other ALK inhibitors.
Article
Oncology
D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James C. H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Maria Rosario Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Scott N. Gettinger, Marcello Tiseo, Huamao M. Lin, Yuyin Liu, Florin Vranceanu, Huifeng Niu, Pingkuan Zhang, Sanjay Popat
Summary: In the final analysis of ALTA-1L study, brigatinib continued to demonstrate superior efficacy and tolerability compared to crizotinib in patients with ALK-positive advanced NSCLC, regardless of poor prognostic biomarkers. The potential survival benefit of brigatinib in patients with brain metastases warrants further investigation.
JOURNAL OF THORACIC ONCOLOGY
(2021)
Article
Oncology
Giulia Mura, Elif Karaca Atabay, Matteo Menotti, Cinzia Martinengo, Chiara Ambrogio, Gloria Giacomello, Maddalena Arigoni, Martina Olivero, Raffaele A. Calogero, Roberto Chiarle, Claudia Voena
Summary: Anaplastic Large Cell Lymphoma (ALCL) is driven by the chimeric tyrosine kinase NPM-ALK, which downregulates the expression of CD45 via STAT3 and acts as a rheostat of ALK oncogenic signaling and resistance to TKI treatment. CD45 is a key regulator of T cell activation and cytokine responses through the JAK/STAT pathway. In ALK+ ALCL, NPM-ALK inhibits T cell molecules expression and activates surrogate TCR signaling. Inhibition of NPM-ALK kinase activity leads to increased expression of CD45RO isoform. Knocking-out CD45 results in increased resistance to ALK TKI treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Shaowen Xie, Yuan Sun, Yulin Liu, Xinnan Li, Xinuo Li, Wenyi Zhong, Feiyan Zhan, Jingjie Zhu, Hong Yao, Dong-Hua Yang, Zhe-Sheng Chen, Jinyi Xu, Shengtao Xu
Summary: Novel ALK degraders based on PROTAC technology showed high specificity in ALK-positive cell lines and significant anti-tumor effects in a mouse model, indicating potential benefits for treating ALK-driven malignancies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Mei-ting Chen, Xiao-hong Fu, He Huang, Zhao Wang, Xiao-jie Fang, Yu-Yi Yao, Quan-Guang Ren, Ze-geng Chen, Tong-yu Lin
Summary: The combination of crizotinib with chemotherapy may be effective in ALK-positive and crizotinib sensitive r/r sALCL patients, with significantly improved progression-free survival rates and overall survival rates within two years compared to the control group.
LEUKEMIA & LYMPHOMA
(2021)
Review
Medicine, General & Internal
Kuan-Li Wu, Hsiao-Ling Chen, Ying-Ming Tsai, Tai-Huang Lee, Hsiu-Mei Chang, Yu-Chen Tsai, Cheng-Hao Chuang, Yong-Chieh Chang, Yu-Kang Tu, Chih-Jen Yang, Jen-Yu Hung, Inn-Wen Chong
Summary: This study compared newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Results showed that ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. Additionally, low-dose alectinib exhibited efficacy similar to a higher dose regimen in Asian populations.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Hematology
Elif Karaca Atabay, Carmen Mecca, Qi Wang, Chiara Ambrogio, Ines Mota, Nina Prokoph, Giulia Mura, Cinzia Martinengo, Enrico Patrucco, Giulia Leonardi, Jessica Hossa, Achille Pich, Luca Mologni, Carlo Gambacorti-Passerini, Laurence Brugieres, Birgit Geoerger, Suzanne D. Turner, Claudia Voena, Taek-Chin Cheong, Roberto Chiarle
Summary: This study identified PTPN1 and PTPN2 phosphatases as drivers of resistance to ALK TKIs in ALK(+) ALCL. These phosphatases regulate ALK phosphorylation and activity, and their loss leads to TKI resistance. Furthermore, SHP2 is a key mediator of oncogenic ALK signaling, and PTPN1 acts as a phosphatase for SHP2. Combination therapy with a SHP2 inhibitor can overcome TKI resistance in ALK(+) ALCL.
Article
Oncology
V. Subbiahy, S. Kuraviy, S. Ganguly, D. R. Welch, C. J. Vivian, M. U. Mushtaq, A. Hegde, S. Iyer, A. Behrang, S. M. Ali, R. W. Madison, J. M. Venstrom, R. A. Jensen, J. P. McGuirk, H. M. Amin, R. Balusu
Summary: The study demonstrates that Ceritinib shows inhibitory effects on the fusion kinase NPM1-ALK and induces apoptosis of lymphoma cells in vitro and in vivo. Treatment with Ceritinib in the NPM1-ALKthorn ALCL xenograft model resulted in tumor regression and improved survival. Among 19,272 patients sequenced, 0.30% harbored ALK fusions, including various hematologic malignancies.
Article
Immunology
Annkristin Heine, Stefanie Andrea Erika Held, Solveig Nora Daecke, Chrystel Flores, Peter Brossart
Summary: This study investigates the immunosuppressive effects of two different ALK inhibitors on dendritic cells. The results show that crizotinib significantly suppresses the activation, migration, and cytokine production of dendritic cells, while alectinib has lesser immunosuppressive effects.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Izzet Dogan, Mustafa Gurbuz, Nail Paksoy, Ferhat Ferhatoglu, Sezai Vatansever, Pinar Saip, Ahmet Demirkazik, Adnan Aydiner
Summary: This study investigated the factors affecting the response of patients with ALK-positive metastatic NSCLC to treatment with ALK inhibitors. The researchers found that the ratio of ALK positivity, gender, and the total number of metastatic sites were predictors of response to ALK inhibitors. Furthermore, they determined that a cutoff level of 33% ALK positivity was associated with objective response.
Article
Oncology
Makoto Nishio, Tatsuya Yoshida, Toru Kumagai, Toyoaki Hida, Ryo Toyozawa, Tadasuke Shimokawaji, Koichi Goto, Kazuhiko Nakagawa, Yuichiro Ohe, Takashi Seto, Kentarou Kudou, Takayuki Asato, Pingkuan Zhang, Nobuyuki Yamamoto
Summary: This study evaluated the efficacy and safety of brigatinib in Japanese patients with ALK-positive NSCLC refractory to alectinib, showing clinically meaningful efficacy and consistent safety profile with broader populations. Brigatinib demonstrated antitumor activity in patients with specific secondary mutations and a significant objective response rate in alectinib-refractory patients.
JOURNAL OF THORACIC 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
Pharmacology & Pharmacy
Meiling Zhang, Qian Wang, Zihao Ke, Yijing Liu, Huijin Guo, Shencun Fang, Kaihua Lu
Summary: The study revealed that LINC01001 is highly expressed in crizotinib-resistant NSCLC cells and correlates with poor overall survival in patients. Inhibition of LINC01001 or IGF2BP2 can suppress NSCLC resistance to crizotinib, indicating that LINC01001 promotes resistance to crizotinib in NSCLC by modulating the IGF2BP2/MYC axis.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Urology & Nephrology
Marco Bonilla, Kenar D. Jhaveri, Hassan Izzedine
Summary: This review introduces the main treatment method, ALK inhibitors, for NSCLC patients with ALK gene rearrangement or ROS1 oncogene fusion. However, the toxic side effects of these drugs, especially those related to the kidneys, need to be taken seriously.
CLINICAL KIDNEY JOURNAL
(2022)
Article
Oncology
Juergen Wolf, Edward B. Garon, Harry J. M. Groen, Daniel S. W. Tan, Isabelle Gilloteau, Sylvie Le Mouhaer, Marcio Hampe, Can Cai, Andrea Chassot-Agostinho, Maria Reynolds, Bintu Sherif, Rebecca S. Heist
Summary: Capmatinib, a MET inhibitor, showed significant antitumour activity and manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC). This study reported the patient-reported outcomes (PROs) of capmatinib treatment, which demonstrated improvements in cough and quality of life (QoL) in these patients, supporting the use of capmatinib in METex14-mutated aNSCLC.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Christoffer T. Maansson, Sofie Helstrup, Eva B. F. Ebert, Peter Meldgaard, Boe S. Sorensen
Summary: This study discovers novel circulating biomarkers that can predict the overall survival after progressive disease (PD) on osimertinib treatment in non-small-cell lung cancer patients with EGFR mutations. The altered expression of immune system-related proteins at PD provides insight into osimertinib resistance.
TRANSLATIONAL LUNG CANCER RESEARCH
(2023)
Review
Oncology
Benjamin P. Levy, Enriqueta Felip, Martin Reck, James C. H. Yang, Federico Cappuzzo, Yasuto Yoneshima, Caicun Zhou, Siddhartha Rawat, Jingdong Xie, Priyanka Basak, Lu Xu, Jacob Sands
Summary: The TROPION-Lung08 study is a Phase III trial evaluating the safety and efficacy of Dato-DXd plus pembrolizumab versus pembrolizumab monotherapy for advanced/metastatic NSCLC patients without AGAs and with PD-L1 tumor proportion score =50%. The primary endpoints are progression-free survival and overall survival, while secondary endpoints include objective response rate, duration of response, safety, and presence of antidrug antibodies.
Article
Oncology
Marina C. Garassino, Shirish Gadgeel, Giovanna Speranza, Enriqueta Felip, Emilio Esteban, Manuel Domine, Maximilian J. Hochmair, Steven F. Powell, Helge G. Bischoff, Nir Peled, Francesco Grossi, Ross R. Jennens, Martin Reck, Rina Hui, Edward B. Garon, Takayasu Kurata, Jhanelle E. Gray, Paul Schwarzenberger, Erin Jensen, M. Catherine Pietanza, Delvys Rodriguez-Abreu
Summary: This study presents the 5-year outcomes of the KEYNOTE-189 study, which included previously untreated metastatic nonsquamous non-small-cell lung cancer patients. The results show that treatment with pembrolizumab plus pemetrexed-platinum significantly improves overall survival and progression-free survival compared to placebo plus pemetrexed-platinum. These data continue to support pembrolizumab plus pemetrexed-platinum as a standard of care for previously untreated metastatic non-small-cell lung cancer patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Gregory J. Riely, Egbert F. Smit, Myung-Ju Ahn, Enriqueta Felip, Suresh S. Ramalingam, Anne Tsao, Melissa Johnson, Francesco Gelsomino, Raymond Esper, Ernest Nadal, Michael Offin, Mariano Provencio, Jeffrey Clarke, Maen Hussain, Gregory A. Otterson, Ibiayi Dagogo-Jack, Jonathan W. Goldman, Daniel Morgensztern, Ann Alcasid, Tiziana Usari, Paul Wissel, Keith Wilner, Nuzhat Pathan, Svitlana Tonkovyd, Bruce E. Johnson
Summary: The combination of encorafenib and binimetinib showed clinical efficacy and acceptable safety in patients with BRAF(V600E)-mutant metastatic NSCLC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
H. Kievit, M. B. Muntinghe-Wagenaar, L. B. M. Hijmering-Kappelle, B. I. Hiddinga, J. F. Ubbels, R. Wijsman, G. Slingers, R. de Vries, H. J. M. Groen, H. A. M. Kerstjens, A. J. van der Wekken, T. J. N. Hiltermann
Summary: This study evaluates the safety and tolerability of Stereotactic radiotherapy combined with double Immune Checkpoint Inhibition (SICI) in advanced non-small cell lung cancer patients. The combination of SBRT and double immunotherapy is shown to be safe and feasible.
Article
Oncology
Christoffer Trier Maansson, Peter Meldgaard, Magnus Stougaard, Anders Lade Nielsen, Boe Sandahl Sorensen
Summary: Cell-free chromatin immunoprecipitation (cfChIP) of H3K36me3-modified nucleosomes in blood plasma can be used to determine tumor gene expression levels. In this study, cfChIP-seq was performed on blood plasma samples from lung cancer patients and healthy controls. The results showed increased enrichment of mutated alleles in plasma from patients with somatic cancer mutations, and concordant H3K36me3 cfChIP enrichment profiles in different lung cancer types. These findings demonstrate the utility of cfDNA in liquid biopsies for characterizing cancer and predicting disease progression.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Haiyan Zeng, Lizza E. L. Hendriks, Willem J. A. Witlox, Harry J. M. Groen, Anne-Marie C. Dingemans, John Praag, Jose Belderbos, Ruud Houben, Vincent van der Noort, Dirk K. M. De Ruysscher
Summary: The aim of this study was to identify risk factors for self-reported cognitive impairment in stage III non-small cell lung cancer (NSCLC) after radical treatment. Cognitive functioning was assessed at seven pre-specified time points using the EORTC-QLQ-C30. The results showed that baseline cognitive impairment was the most important risk factor for subsequent cognitive impairment in stage III NSCLC.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
H. C. Donker, B. van Es, M. Tamminga, G. A. Lunter, L. C. L. T. van Kempen, E. Schuuring, T. J. N. Hiltermann, H. J. M. Groen
Summary: By analyzing DNA mutations in pre-treatment tissue, researchers have identified specific mutational signatures that are associated with response to immunotherapy in advanced non-small cell lung cancer patients. This finding could potentially help select patients who are likely to benefit from immunotherapy.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Theodore S. Kapellos, Kevin Babler, Wataru Fujii, Christina Nalkurthi, Anna C. Schaar, Lorenzo Bonaguro, Tal Pecht, Izabela Galvao, Shobhit Agrawal, Adem Saglam, Erica Dudkin, Amit Frishberg, Elena de Domenico, Arik Horne, Chantal Donovan, Richard Y. Kim, David Gallego-Ortega, Tessa E. Gillett, Meshal Ansari, Jonas Schulte-Schrepping, Nina Offermann, Ignazio Antignano, Burcu Sivri, Wenying Lu, Mathew S. Eapen, Martina van Uelft, Collins Osei-Sarpong, Maarten van den Berge, Hylke C. Donker, Harry J. M. Groen, Sukhwinder S. Sohal, Johanna Klein, Tina Schreiber, Andreas Feisst, Ali Oender Yildirim, Herbert B. Schiller, Martijn C. Nawijn, Matthias Becker, Kristian Haendler, Marc Beyer, Melania Capasso, Thomas Ulas, Jan Hasenauer, Carmen Pizarro, Fabian J. Theis, Philip M. Hansbro, Dirk Skowasch, Joachim L. Schultze
Summary: Systemic inflammation is a characteristic feature of late-stage severe lung disease, while the molecular, functional, and phenotypic changes in peripheral immune cells in the early stages of the disease remain poorly understood. In this study, using single-cell analyses, the researchers found that blood neutrophils are already increased in early-stage COPD, and the changes in their molecular and functional states correlate with the decline of lung function. Further investigation using a murine cigarette smoke exposure model revealed similar molecular changes in blood neutrophils and precursor populations in the blood and lung. The findings suggest that systemic molecular alterations in neutrophils and their precursors are present in the early stages of COPD, and may serve as potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
Article
Oncology
Peter Meldgaard, Michael Kristensen, Simona Conte, Klaus Kaae Andersen, Aleksander Jovanovic, Ebbe Meldgaard
Summary: Despite advancements in treatment strategies for NSCLC, there is still an unmet need for patients. This retrospective cohort study aimed to provide real-world knowledge about patient characteristics, treatment patterns, and survival outcomes in NSCLC patients at Aarhus University Hospital in Denmark.
Article
Oncology
Karin Holmskov Hansen, Jakob Sidenius Johansen, Edyta Maria Urbanska, Peter Meldgaard, Peter Hjorth-Hansen, Charlotte Kristiansen, Miroslaw Stelmach, Eric Santoni-Rugiu, Maiken Parm Ulhoi, Anders Bondo Dydensborg, Christina Dunweber, Jon Lykkegaard Andersen
Summary: This study investigates the treatment and clinical outcomes of ALK+ NSCLC patients in Denmark and confirms the superior disease control provided by second generation ALK-TKIs compared to the first generation ALK-TKI crizotinib.
Review
Oncology
Fenneke Zwierenga, Bianca A. M. H. van Veggel, Anke Van den Berg, Harry J. M. Groen, Lili Zhang, Matthew R. Groves, K. Kok, E. F. Smit, T. Jeroen N. Hiltermann, Adrianus J. de Langen, Anthonie J. Van der Wekken
Summary: This article provides a comprehensive assessment of drug sensitivity in vitro and in clinical settings for EGFRex20+ mutations in NSCLC. The activating A763_Y764insFQEA mutation shows better tumor response compared to mutations in other regions, suggesting the need for different treatment approaches. Classification beyond exon-based categories is necessary due to marked differences in treatment responses among EGFRex20+ mutations.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Ebbe Meldgaard Uldbjerg, Lars Ringgaard, Klaus Kaae Andersen, Line Elmerdahl Frederiksen, Aleksandar Jovanovic, Peter Meldgaard
Summary: This study provides important insights into the long-term follow-up of disease-free survival (DFS) and recurrence patterns in early-stage non-small-cell lung cancer (NSCLC) patients. Despite improvements in DFS, disease relapse remains a significant challenge, highlighting the need for better treatment strategies.
Review
Radiology, Nuclear Medicine & Medical Imaging
Yifei Mao, Jiali Cai, Marjolein A. Heuvelmans, Rozemarijn Vliegenthart, Harry J. M. Groen, Matthijs Oudkerk, Marleen Vonder, Monique D. Dorrius, Geertruida H. de Bock
Summary: This systematic review and meta-analysis evaluated the performance of Lung-RADS (versions 1.0 and 1.1) in detecting lung cancer in different populations. The results showed that studies in high-risk populations had higher sensitivity and lower specificity than studies in general populations. Non-Asian studies tended to have better diagnostic performance than Asian studies. Limited evidence was available for the performance of Lung-RADS version 1.1 and its applicability to Asian populations.
EUROPEAN RADIOLOGY
(2023)