Review
Oncology
Silvia Novello, Raffaele Califano, Niels Reinmuth, Antonella Tamma, Tarun Puri
Summary: This review provides a summary of available therapies for RET fusion-positive NSCLC, evaluating their efficacy and safety as well as primary and secondary resistance mechanisms. RET-selective inhibitors are recommended as first-line therapy options for these patients.
Review
Oncology
Silvia Novello, Raffaele Califano, Niels Reinmuth, Antonella Tamma, Tarun Puri
Summary: This narrative review aims to summarize the efficacy and safety of available therapies for RET fusion-positive non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases. It provides background information on RET rearrangements in NSCLC and molecular testing options, along with an overview of clinical guidelines for broad molecular testing. The review discusses the efficacy and safety of potential treatments, including multikinase inhibitors, RET-selective inhibitors, pemetrexed-based therapy, and immunotherapies, and highlights RET-selective inhibitors as preferred first-line therapy options for RET fusion-positive metastatic NSCLC.
Article
Medicine, Research & Experimental
Chunyue Wang, Zhenlong Zhang, Yulan Sun, Song Wang, Mengmeng Wu, Qiuxiang Ou, Yang Xu, Zhiming Chen, Yang Shao, Hong Liu, Peifeng Hou
Summary: This study depicted the mutational profiles of NSCLC patients with RET fusions at baseline or after resistance to EGFR-TKIs. The results suggest that RET fusions may mediate secondary resistance to third-generation EGFR-TKIs and could be associated with poor prognosis in patients with NSCLC.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Priscilla Cascetta, Vincenzo Sforza, Anna Manzo, Guido Carillio, Giuliano Palumbo, Giovanna Esposito, Agnese Montanino, Raffaele Costanzo, Claudia Sandomenico, Rossella De Cecio, Maria Carmela Piccirillo, Carmine La Manna, Giuseppe Totaro, Paolo Muto, Carmine Picone, Roberto Bianco, Nicola Normanno, Alessandro Morabito
Summary: RET rearrangements in NSCLC act as a potential therapeutic target, with selective RET inhibitors showing higher efficacy rates and good tolerability, providing hope for patients with RET-positive NSCLC. Ongoing phase III clinical trials will definitively establish the efficacy of these inhibitors in RET-positive NSCLC patients.
Article
Oncology
Shinji Takeuchi, Noriko Yanagitani, Takashi Seto, Yoshihiro Hattori, Kadoaki Ohashi, Masahiro Morise, Shingo Matsumoto, Kiyotaka Yoh, Koichi Goto, Makoto Nishio, Shizuko Takahara, Takahiro Kawakami, Yasuhito Imai, Kenichi Yoshimura, Azusa Tanimoto, Akihiro Nishiyama, Toshinori Murayama, Seiji Yano
Summary: The study suggests limited activity of alectinib against RET-rearranged NSCLC, with an objective response rate of 4% and a median progression-free survival of 3.4 months. Further research is needed to improve outcomes for these patients.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Review
Oncology
Zixiong Shen, Binxu Qiu, Lin Li, Bo Yang, Guanghu Li
Summary: This review provides an overview of the characteristics and fusion methods of RET genes, analyzes the advantages and disadvantages of different detection methods for RET fusions, summarizes the recent application of non-selective and selective RET fusion-positive inhibitors, and discusses the mechanisms and coping strategies of resistance to these inhibitors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Hiroki Izumi, Shingo Matsumoto, Jie Liu, Kosuke Tanaka, Shunta Mori, Kumiko Hayashi, Shogo Kumagai, Yuji Shibata, Takuma Hayashida, Kana Watanabe, Tatsuro Fukuhara, Takaya Ikeda, Kiyotaka Yoh, Terufumi Kato, Kazumi Nishino, Atsushi Nakamura, Ichiro Nakachi, Shoichi Kuyama, Naoki Furuya, Jun Sakakibara-Konishi, Isamu Okamoto, Kageaki Taima, Noriyuki Ebi, Haruko Daga, Akira Yamasaki, Masahiro Kodani, Hibiki Udagawa, Keisuke Kirita, Yoshitaka Zenke, Kaname Nosaki, Eri Sugiyama, Tetsuya Sakai, Tokiko Nakai, Genichiro Ishii, Seiji Niho, Atsushi Ohtsu, Susumu S. Kobayashi, Koichi Goto
Summary: Lung cancer is a highly aggressive tumor type, and targeted therapies based on oncogenic drivers have greatly improved outcomes for patients with non-small-cell lung cancer (NSCLC). However, a significant percentage of lung adenocarcinoma cases lack known oncogenic drivers, and the identification of the CLIP1-LTK fusion as a potential target in NSCLC represents a novel finding with therapeutic implications.
Article
Oncology
Youngkyung Jeon, Hyun Ae Jung, Sehhoon Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Se-Hoon Lee
Summary: This study evaluated the efficacy and safety of pralsetinib in advanced non-small cell lung cancer patients with RET rearrangement. The results showed that pralsetinib demonstrated clinical benefit in patients with RET-rearranged NSCLC, along with an acceptable safety profile.
CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Ming Gao, Xia Zhang, Huan Yan, Decong Sun, Xuejiao Yang, Fang Yuan, Yanfang Ju, Lijie Wang, Jinliang Wang, Wei Zhao, Dong Zhang, Lin Li, Xiaoyun Xu, Junxun Ma, Yi Hu, Xiaotao Zhang
Summary: RET oncogene is an important target in non-small cell lung cancer. Pralsetinib is efficacious in patients with RET fusion-positive NSCLC, but may lead to adverse reactions like opportunistic pneumonia. Early recognition and treatment of pneumonia during pralsetinib therapy is crucial for continued benefits.
SUPPORTIVE CARE IN CANCER
(2023)
Review
Biochemistry & Molecular Biology
Danilo Rocco, Luigi Sapio, Luigi Della Gravara, Silvio Naviglio, Cesare Gridelli
Summary: RET-selective tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib have transformed the treatment landscape for RET-positive (RET+) advanced non-small cell lung cancer (NSCLC) due to their effectiveness and safety profiles. However, there is still limited understanding of resistance mechanisms after treatment with these TKIs. Chemotherapy +/- immunotherapy is currently recommended as a second-line treatment for patients progressing on selpercatinib or pralsetinib. Therefore, further research on the resistance mechanisms triggered by RET-TKIs is crucial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sara Elena Rebuzzi, Lodovica Zullo, Giovanni Rossi, Massimiliano Grassi, Veronica Murianni, Marco Tagliamento, Arsela Prelaj, Simona Coco, Luca Longo, Maria Giovanna Dal Bello, Angela Alama, Chiara Dellepiane, Elisa Bennicelli, Umberto Malapelle, Carlo Genova
Summary: In the systemic treatment of advanced NSCLC patients, targeted therapies such as EGFR, ALK, ROS1, and BRAF inhibitors have been significant breakthroughs. In addition to these known molecular drivers, potential therapeutic targets including MET, RET, NTRK, KRAS, PIK3CA, and HER2 are rapidly emerging. Research on these emerging molecular targets is crucial to increasing the proportion of patients benefiting from tailored therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Lu Zhao, Qingyun Mei, Yongchao Yu, Na Wang, Dou Zhang, Dongying Liao, Jinhui Zuo, Hongxia Xie, Yingjie Jia, Fanming Kong
Summary: Significant progress has been made in the treatment of driver gene-positive Non-Small Cell Lung Cancer (NSCLC) in recent years. RET fusion, which occurs in 0.7% to 2% of NSCLC cases, is associated with a younger age and never-smoker status. The use of pralsetinib and selpercatinib for RET fusion NSCLC is recommended according to the 2021 NSCLC treatment guidelines. This review summarizes the research progress, current challenges, and proposals for improving the outlook for patients with RET fusion NSCLC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Antonio Passaro, Giuseppe Lo Russo, Francesco Passiglia, Manolo D'Arcangelo, Andrea Sbrana, Marco Russano, Laura Bonanno, Raffaele Giusti, Giulio Metro, Federica Bertolini, Salvatore Grisanti, Annamaria Carta, Fabiana Cecere, Michele Montrone, Giacomo Massa, Fabiana Perrone, Francesca Simionato, Giorgia Guaitoli, Vieri Scotti, Carlo Genova, Antonio Lugini, Lucia Bonomi, Ilaria Attili, Filippo de Marinis
Summary: In the real-world setting, pralsetinib demonstrated durable systemic activity and intracranial response in patients with RET-fusion positive NSCLC. The toxicity profile of pralsetinib was consistent with previous reports.
Article
Oncology
Qing Zhou, Jun Zhao, Jianhua Chang, Huijie Wang, Yun Fan, Ke Wang, Gang Wu, Weiqi Nian, Yuping Sun, Meili Sun, Xiangcai Wang, Huaqiu Shi, Xiangqian Zheng, Sheng Yao, Mengmeng Qin, Zhenwei Shen, Jason Yang, Yi-Long Wu
Summary: The efficacy and safety of pralsetinib were evaluated in Chinese patients with advanced RET fusion-positive non-small cell lung cancer. Pralsetinib demonstrated robust and durable clinical activity with a well-tolerated safety profile in both pretreated and treatment-naive patients.
Review
Oncology
Leylah M. Drusbosky, Estelamari Rodriguez, Richa Dawar, Chukwuemeka V. Ikpeazu
Summary: Recent FDA approvals for tumor-agnostic drugs have shifted cancer treatment from organ/histology-specific strategies to biomarker-guided approaches. RET gene fusions, known oncogenic drivers in various tumors, can be effectively targeted by inhibitors like selpercatinib and pralsetinib, showing significant clinical benefits in NSCLC patients.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Surgery
David Belzile, Pierre Yves Turgeon, Evelyne Leblanc, Montse Massot, Christine Bourgault, Joelle Morin, Celine Dupuis, Marc Bilodeau, Maxime Laflamme, Eric Charbonneau, Sylvain Trahan, Sylvain Page, Philippe Joubert, Christian Couture, Mario Senechal
Summary: This study aimed to explore the diagnostic value of liver disease detection in diagnosing cirrhosis in patients with advanced heart failure. The results showed that ultrasound has the best sensitivity and specificity, but more than a third of patients with cirrhosis will go undiagnosed.
CLINICAL TRANSPLANTATION
(2021)
Article
Multidisciplinary Sciences
Romain Villot, Audrey Poirier, Inan Bakan, Karine Boulay, Erlinda Fernandez, Romain Devillers, Luciano Gama-Braga, Laura Tribouillard, Andreanne Gagne, Ema Duchesne, Danielle Caron, Jean-Sebastien Berube, Jean-Christophe Berube, Yan Coulombe, Michele Orain, Yves Gelinas, Stephane Gobeil, Yohan Bosse, Jean-Yves Masson, Sabine Elowe, Steve Bilodeau, Venkata Manem, Philippe Joubert, Frederick A. Mallette, Mathieu Laplante
Summary: The study reveals that RAS activation destabilizes the transcription factor ZNF768, leading to cellular senescence by derepression of the p53 pathway; Overexpression of ZNF768 can bypass RAS-induced senescence and promote proliferation; ZNF768 is often overexpressed in tumors, suggesting its role in evading senescence and promoting malignant transformation.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Julie Niogret, Helene Berger, Cedric Rebe, Romain Mary, Elise Ballot, Caroline Truntzer, Marion Thibaudin, Valentin Derangere, Christophe Hibos, Lea Hampe, David Rageot, Theo Accogli, Philippe Joubert, Bertrand Routy, James Harker, Frederique Vegran, Francois Ghiringhelli, Fanny Chalmin
Summary: Tfh cells play an important role in antitumor immune response, especially in a CD8(+)-dependent manner, by producing interleukin-21 to support the function of exhausted T cells. Their accumulation in tumor sites and draining lymph nodes is closely associated with treatment efficacy and patient survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Audrey Poirier, Andreanne Gagne, Philippe Laflamme, Meagan Marcoux, Michele Orain, Sophie Plante, David Joubert, Philippe Joubert, Mathieu Laplante
Summary: Zinc-finger protein 768 (ZNF768) is overexpressed in LUAD and correlates with proliferative features, supporting its role in promoting cancer cell proliferation in humans.
Article
Biology
Kim Valette, Zhonglin Li, Valentin Bon-Baret, Arnaud Chignon, Jean-Christophe Berube, Aida Eslami, Jennifer Lamothe, Nathalie Gaudreault, Philippe Joubert, Ma'en Obeidat, Maarten van den Berge, Wim Timens, Don D. Sin, David C. Nickle, Ke Hao, Catherine Labbe, Krystelle Godbout, Andreanne Cote, Michel Laviolette, Louis-Philippe Boulet, Patrick Mathieu, Sebastien Theriault, Yohan Bosse
Summary: The study identified 72 asthma-associated loci and potential therapeutic targets through GWAS, TWAS, and Mendelian randomization. Blood showed the largest fold enrichment of regulatory and functional annotations among asthma-associated variants. Among 485 blood eQTL-regulated genes associated with asthma, 50 were confirmed to be causal.
COMMUNICATIONS BIOLOGY
(2021)
Editorial Material
Oncology
Philippe Joubert, William D. Travis
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Pathology
Jamal K. Benhamida, Monika Vyas, Atsushi Tanaka, Lu Wang, Armita Bahrami, Kerem Ozcan, Olca Basturk, Liliana Villafania, Douglas A. Mata, Tony El Jabbour, Pier Selenica, Michael H. A. Roehrl, Britta Weigelt, J. S. Reis-Filho, Scaltriti Maurizio, David S. Klimstra
Summary: Pancreatic neoplasms are classified by lines of differentiation, with genome methylation signatures increasingly used for classification support. Epigenetic relationships suggest similarities between acinar cell carcinomas and pancreatoblastomas, with mixed acinar neoplasms more closely related to pure acinar cell carcinomas.
Article
Oncology
Wenqing Qi, Wojciech Rosikiewicz, Zhaohong Yin, Beisi Xu, Huihong Jiang, Shibiao Wan, Yiping Fan, Gang Wu, Lu Wang
Summary: Mesenchymal chondrosarcoma is a rare and aggressive primitive mesenchymal tumor that mainly affects adolescents and young adults. Researchers have identified the fusion protein HEY1-NCOA2, which promotes cell proliferation and upregulates the expression of PDGFB and PDGFRA, providing a potential target for treating mesenchymal chondrosarcoma.
JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Jan Barinka, Zunsong Hu, Lu Wang, David A. Wheeler, Delaram Rahbarinia, Clay McLeod, Zhaohui Gu, Charles G. Mullighan
Summary: In this study, the authors describe a method called RNAseqCNV for detecting CNVs from RNA-seq data. They used models based on gene expression and minor allele frequency to accurately classify CNVs in ALL and AML. The results showed that RNAseqCNV outperforms other algorithms in detecting CNVs in the ALL dataset and the calls were highly concordant with DNA-based CNV results.
Article
Multidisciplinary Sciences
Mark Sorin, Morteza Rezanejad, Elham Karimi, Benoit Fiset, Lysanne Desharnais, Lucas J. M. Perus, Simon Milette, Miranda W. W. Yu, Sarah M. M. Maritan, Samuel Dore, Emilie Pichette, William Enlow, Andreanne Gagne, Yuhong Wei, Michele Orain, Venkata S. K. Manem, Roni Rayes, Peter M. M. Siegel, Sophie Camilleri-Broet, Pierre Olivier Fiset, Patrice Desmeules, Jonathan D. D. Spicer, Daniela F. F. Quail, Philippe Joubert, Logan A. A. Walsh
Summary: Single-cell technologies have provided unprecedented resolution for understanding the complexity of the tumour immune microenvironment. In this study, imaging mass cytometry was used to analyze samples from 416 patients with lung adenocarcinoma, revealing spatial features of the tumour and immunological landscape. By applying deep learning, the researchers successfully predicted post-surgery progression in patients.
Article
Oncology
Mark Sorin, Elham Karimi, Morteza Rezanejad, Miranda W. Yu, Lysanne Desharnais, Sheri A. C. McDowell, Samuel Dore, Azadeh Arabzadeh, Valerie Breton, Benoit Fiset, Yuhong Wei, Roni Rayes, Michele Orain, Francois Coulombe, Venkata S. K. Manem, Andreanne Gagne, Daniela F. Quail, Philippe Joubert, Jonathan D. Spicer, Logan A. Walsh
Summary: This study used imaging mass cytometry to characterize the tumor and immunological landscape in non-small cell lung cancer patients receiving immunotherapy. They identified cellular states and interactions associated with improved treatment efficacy and found that CXCL13 expression is correlated with treatment response. The results were validated in preclinical mouse models, demonstrating that recombinant CXCL13 enhances anti-PD-1 therapy response.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Patrice Desmeules, Matthieu Dusselier, Cedrik Bouffard, Josee Bafaro, Marc Fortin, Catherine Labbe, Philippe Joubert
Summary: This study evaluated the value of ctDNA NGS as a non-invasive alternative for NSCLC management. The results showed that ctDNA provided additional information but may miss known alterations. Compared to tissue single-gene testing, ctDNA had a shorter turnaround time but limited biomarker coverage.
Article
Oncology
Marie-Helene Denault, Catherine Labbe, Carolle St-Pierre, Brigitte Fournier, Andreanne Gagne, Claudia Morillon, Philippe Joubert, Serge Simard, Simon Martel
Summary: This study reviewed medical records of lung cancer patients in four hospital networks in Quebec, Canada, and found that wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced non-small cell lung cancer and small cell lung cancer might indicate a tendency for clinicians to act quicker on sicker patients.
Article
Medicine, Research & Experimental
Andrew W. Maksymiuk, Paramjit S. Tappia, Rashid Ahmed Bux, Dante Moyer, Guoyu Huang, Philippe Joubert, Donald W. Miller, Bram Ramjiawan, Daniel S. Sitar
Summary: The study aims to assess tumor response to therapy by monitoring changes in plasma acetylamantadine concentrations. Results showed a reduction of approximately 32% in responders and an increase of approximately 34% in nonresponders at the 4-hour collection point. Larger-scale studies are needed, but the test could potentially provide an effective tool for assessing treatment response and improving patient management.
Review
Respiratory System
L. V. Morin-Thibault, D. Wiseman, P. Joubert, R. Paulin, S. Bonnet, S. Provencher
Summary: PTTM is a rare syndrome that presents as progressive dyspnea, pulmonary hypertension and right heart failure. It is associated with a poor prognosis, with most patients dying within days or weeks of their admission. Transbronchial biopsy and pulmonary microvascular cytology may be alternative diagnostic methods, but the best treatment strategy remains unclear.
CANADIAN JOURNAL OF RESPIRATORY CRITICAL CARE AND SLEEP MEDICINE
(2021)