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
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
Jonathan W. Goldman, Lynette M. Sholl, Sanja Dacic, Michael C. Fishbein, Yonina R. Murciano-Goroff, Ravi Rajaram, Sylwia Szymczak, Anna M. Szpurka, Bo H. Chao, Alexander Drilon
Summary: The LIBRETTO-001 trial showed the effectiveness of selpercatinib, a selective rearrangement during transfection (RET) inhibitor, in advanced RET fusion-positive non-small cell lung cancer (NSCLC), leading to its approval for this indication. A cohort study within LIBRETTO-001 was conducted to evaluate neoadjuvant and adjuvant selpercatinib in early-stage RET fusion-positive NSCLC, with the primary goal of major pathologic response. A patient with stage IB KIF5B-RET fusion-positive NSCLC received neoadjuvant selpercatinib for 8 weeks followed by surgery, resulting in a complete pathologic response. This case supports the potential utility of RET inhibitor therapy in early-stage RET fusion-positive NSCLC.
FRONTIERS IN ONCOLOGY
(2023)
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.
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)
Review
Chemistry, Medicinal
Faraat Ali, Kumari Neha, Garima Chauhan
Summary: This review article summarizes the development, chemistry, characteristics, and treatment mechanism of Pralsetinib (PRL), as well as its application in the treatment of various solid tumors.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Review
Chemistry, Medicinal
Faraat Ali, Kumari Neha, Garima Chauhan
Summary: Pralsetinib (PRL) is a novel RET inhibitor used for treatment of specific types of cancers, which has been approved in the United States and Europe. This review article summarizes key information on the development, chemistry, mechanism, pharmacokinetics, and pharmacodynamics of PRL.
ARCHIVES OF PHARMACAL RESEARCH
(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
Cell Biology
Takuo Hayashi, Igor Odintsov, Roger S. Smith, Kota Ishizawa, Allan J. W. Liu, Lukas Delasos, Christopher Kurzatkowski, Huichun Tai, Eric Gladstone, Morana Vojnic, Shinji Kohsaka, Ken Suzawa, Zebing Liu, Siddharth Kunte, Marissa S. Mattar, Inna Khodos, Monika A. Davare, Alexander Drilon, Emily Cheng, Elisa de Stanchina, Marc Ladanyi, Romel Somwar
Summary: The study demonstrates that cabozantinib is effective in targeting lung cancers with RET rearrangements by inhibiting tumor growth and activating specific apoptotic pathways. Additionally, cabozantinib suppresses MYC protein levels induced by RET expression, suggesting new therapeutic strategies for RET fusion-driven lung cancers. The novel RET fusion-dependent preclinical models offer valuable tools for refining current therapies and exploring new treatment approaches.
DISEASE MODELS & MECHANISMS
(2021)
Article
Oncology
Shun Lu, Ying Cheng, Dingzhi Huang, Yuping Sun, Lin Wu, Chengzhi Zhou, Ye Guo, Jingxin Shao, Wanli Zhang, Jianying Zhou
Summary: This study evaluated the efficacy and safety of selpercatinib in Chinese patients with RET fusion-positive NSCLC. The results showed that selpercatinib demonstrated durable and effective antitumor activity against RET fusion-positive NSCLC, with good tolerability, consistent with previous findings.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)
Review
Oncology
Chang Lu, Qing Zhou
Summary: This article summarizes the current hot topic of selective RET inhibitors and outlines the utility of various diagnostic techniques, as well as the management evidence for RET fusion-positive NSCLC patients, including specific patient groups and mechanisms of acquired resistance.
CANCER TREATMENT REVIEWS
(2021)
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.
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
Oncology
Benjamin J. Solomon, Cai Cun Zhou, Alexander Drilon, Keunchil Park, Jurgen Wolf, Yasir Elamin, Hannah M. Davis, Victoria Soldatenkova, Andreas Sashegyi, Aimee Bence Lin, Boris K. Lin, Herbert H. Loong, Silvia Novello, Edurne Arriola, Maurice Perol, Koichi Goto, Fernando C. Santini
Summary: Selpercatinib, a highly selective RET inhibitor, demonstrated clinically meaningful antitumor activity with manageable toxicity in RET fusion-positive non-small-cell lung cancer patients. The ongoing Phase III trial, LIBRETTO-431, is evaluating selpercatinib versus chemotherapy in treatment-naive patients with RET fusion-positive nonsquamous non-small-cell lung cancer, with progression-free survival as the primary endpoint.
