Review
Oncology
Yu Lei, Yan Lei, Xiang Shi, Jingjing Wang
Summary: Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate, and the EML4-ALK fusion gene is one of the most important pathogenic driver genes of NSCLC. With the development of molecular targeted research, the introduction of four generations of targeted drugs for EML4-ALK has significantly benefited patients.
Article
Biology
Shinichi Namba, Toshihide Ueno, Shinya Kojima, Kenya Kobayashi, Katsushige Kawase, Yosuke Tanaka, Satoshi Inoue, Fumishi Kishigami, Shusuke Kawashima, Noriko Maeda, Tomoko Ogawa, Shoichi Hazama, Yosuke Togashi, Mizuo Ando, Yuichi Shiraishi, Hiroyuki Mano, Masahito Kawazu
Summary: The MuSTA pipeline enables efficient transcriptome assembly from long-read sequencing data of breast cancer samples, leading to the discovery of subtype-specific isoforms and genomic context-dependent fusion transcript structures. This method sheds light on the influence of chromosomal structural alterations on cancer transcriptomes.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yi-Lin Chen, Wan-Li Chen, Yi-Chia Cheng, Ming-Ching Lin, Shu-Ching Yang, Hung-Wen Tsai, Chien-Chung Lin, Wu-Chou Su, Nan-Haw Chow, Chung-Liang Ho
Summary: A novel RNA-based ALK KD analysis was developed for screening ALK rearrangement in MPE and FFPE specimens of NSCLC. The test showed high sensitivity and specificity when compared with ALK IHC, making it a desirable screening tool with potential for routine diagnostics.
Article
Oncology
Leora Horn, Ziping Wang, Gang Wu, Elena Poddubskaya, Tony Mok, Martin Reck, Heather Wakelee, Alberto A. Chiappori, Dae Ho Lee, Valeriy Breder, Sergey Orlov, Irfan Cicin, Ying Cheng, Yunpeng Liu, Yun Fan, Jennifer G. Whisenant, Yi Zhou, Vance Oertel, Kim Harrow, Chris Liang, Li Mao, Giovanni Selvaggi, Yi-Long Wu
Summary: Ensartinib demonstrated superior efficacy compared to crizotinib in both systemic and intracranial disease, making it a new first-line option for patients with ALK-positive NSCLC.
Article
Critical Care Medicine
Benjamin J. Solomon, Todd M. Bauer, Tony S. K. Mok, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Yi-Long Wu, Jacek Jassem, Froylan Lopez Lopez, Ross A. Soo, Alice T. Shaw, Anna Polli, Rossella Messina, Laura Iadeluca, Francesca Toffalorio, Enriqueta Felip
Summary: After 3 years of follow-up, lorlatinib showed durable benefit over crizotinib in treatment-naive ALK-positive non-small-cell lung cancer patients, indicating the potential use of lorlatinib as a first-line treatment option.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Oncology
Keiko Tanimura, Tadaaki Yamada, Koutaroh Okada, Kunihiro Nakai, Mano Horinaka, Yuki Katayama, Kenji Morimoto, Yuri Ogura, Takayuki Takeda, Shinsuke Shiotsu, Kosuke Ichikawa, Satoshi Watanabe, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Hirokazu Taniguchi, Kazue Yoneda, Satoaki Matoba, Toshiyuki Sakai, Hisanori Uehara, Seiji Yano, Tetsuro Kusaba, Ryohei Katayama, Koichi Takayama
Summary: This study elucidates the pivotal role of HER3 activation in the emergence of drug-tolerant cells in ALK-rearranged lung cancer, and finds that inhibiting HER3 signals combined with ALK-TKI treatment dramatically improves outcomes in ALK-rearranged lung cancer with mesenchymal features.
NPJ PRECISION ONCOLOGY
(2022)
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)
Article
Oncology
Xiaoqian Zhai, Qiang Wu, Dan Pu, Liyuan Yin, Weiya Wang, Daxing Zhu, Feng Xu
Summary: A novel ALK fusion partner (ALK-GCA) and its sensitivity to alectinib in lung cancer were reported, highlighting the importance of detecting fusion mutations and reporting their response to guide treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jiuzhou Zhao, Xiang Li, Ruizhe Fan, Yaping Qin, Zhizhong Wang, Bo Wang, Shaomei Li, Jianfeng Fan, Xinxin Wu, Hongxia Liu, Yuping Guan, Yinfeng Liang, Xiao Zhang, Yongjun Guo
Summary: Primary drug resistance to first- and second-generation ALK inhibitors in NSCLC patients with ALK rearrangement may be caused by de novo ALK kinase domain mutations.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Savvas Papageorgiou, Sarah L. Pashley, Laura O'Regan, Sam Khan, Richard Bayliss, Andrew M. Fry
Summary: Lung cancer is a common and difficult-to-treat cancer. The EML4-ALK protein has been identified as a driving factor in a subset of lung cancer cases. While targeted inhibitors of ALK have shown initial effectiveness, resistance to these drugs develops over time. This review explores the resistance mechanisms and alternative treatment options for EML4-ALK-positive lung cancer patients, including approaches that target ALK-dependent signaling pathways and combination therapies.
Article
Oncology
Sarang S. Talwelkar, Mikko I. Mayranpaa, Julia Schuler, Nora Linnavirta, Annabrita Hemmes, Simone Adinolfi, Matti Kankainen, Wolfgang Sommergruber, Anna-Liisa Levonen, Jari Rasanen, Aija Knuuttila, Emmy W. Verschuren, Krister Wennerberg
Summary: Treatment with ALK inhibitors improves outcome for NSCLC patients with ALK-rearranged tumors, but resistance typically develops. In this study, tumor cell cultures were generated from an ALK-rearranged tumor specimen and drug screens identified a role for PI3K beta and EGFR inhibition in enhancing ALK-inhibitor response and preventing resistance. Combinatorial treatment with ALK and PI3K beta inhibitors showed promise in targeting ALK-rearranged NSCLC.
MOLECULAR ONCOLOGY
(2023)
Article
Respiratory System
Ying Li, Yongwen Li, Hongbing Zhang, Ruifeng Shi, Zihe Zhang, Hongyu Liu, Jun Chen
Summary: The study revealed that aberrant expression of EML4-ALK leads to activation of the JAK2-STAT signaling pathway, essential for the development of non-small cell lung cancer. Inhibiting EML4-ALK resulted in increased apoptosis in lung cancer cells, while overexpression of EML4-ALK increased cell viability. Additionally, treatment with ALK or JAK-STAT pathway inhibitors significantly decreased cell viability in EML4-ALK-positive lung cancer cells.
BMC PULMONARY MEDICINE
(2021)
Review
Respiratory System
Danilo Rocco, Luigi Della Gravara, Ciro Battiloro, Cesare Gridelli
Summary: This article provides a comprehensive review of first-line approved ALK-tyrosine-kinase inhibitors (ALK-TKIs) and discusses the development of ALK-TKIs to overcome resistance mutations. Alectinib is currently considered the standard of care for first-line treatment of ALK+ NSCLC, and lorlatinib and ensartinib are the most promising new drugs.
EXPERT REVIEW OF RESPIRATORY MEDICINE
(2022)
Article
Oncology
Kai Ou, Xiu Liu, Weihua Li, Yi Yang, Jianming Ying, Lin Yang
Summary: This study reported a 34-year-old patient with ALK rearrangement-positive and KRAS-wild pancreatic cancer, who showed significant responses to targeted therapies after developing resistance to chemotherapy, indicating that comprehensive molecular profiling for guiding targeted therapies can significantly improve survival outcomes for a subgroup of patients with pancreatic cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Chang Liu, Cuicui Liu, Jiatao Liao, Jiani C. Yin, Xianghua Wu, Xinmin Zhao, Si Sun, Huijie Wang, Zhihuang Hu, Yao Zhang, Hui Yu, Yang Shao, Jialei Wang
Summary: In this study, the mutational landscape of ALK-positive advanced NSCLCs both at baseline and disease progression was profiled, and resistance mechanisms and molecular correlations of progression-free survival (PFS) in response to first-line crizotinib were characterized. Rational selection of subsequent ALK TKIs may be facilitated by these findings.
