Article
Biochemistry & Molecular Biology
Kwang-Hyeok Kim, Jin-Ock Kim, Jeong-Yang Park, Min-Duk Seo, Sang Gyu Park
Summary: Lung cancer is a major cause of cancer-related deaths, with small cell lung cancer (SCLC) accounting for a significant portion. Overexpression of c-Kit is a characteristic of SCLC. This study found that the antibody-drug conjugate 4C9-DM1 shows potential as a therapeutic agent for SCLC, as it efficiently induces apoptosis and inhibits tumor growth. Combination treatment with other drugs further enhances its anti-tumor effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Bob T. Li, Egbert F. Smit, Yasushi Goto, Kazuhiko Nakagawa, Hibiki Udagawa, Julien Mazieres, Misako Nagasaka, Lyudmila Bazhenova, Andreas N. Saltos, Enriqueta Felip, Jose M. Pacheco, Maurice Perol, Luis Paz-Ares, Kapil Saxena, Ryota Shiga, Yingkai Cheng, Suddhasatta Acharyya, Patrik Vitazka, Javad Shahidi, David Planchard, Pasi A. Janne
Summary: Trastuzumab deruxtecan demonstrated durable anticancer activity in previously treated HER2-mutant NSCLC patients, with two cases of fatal drug-related interstitial lung disease reported. The observed toxic effects were generally consistent with previous studies.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Nicholas McNamee, Ines Pires da Silva, Adnan Nagrial, Bo Gao
Summary: Small-cell lung cancer (SCLC) is an aggressive disease with limited treatment options and poor survival rates. While there have been significant advancements in the treatment of non-small cell lung cancer (NSCLC), SCLC has not seen the same level of progress. This is due, in part, to the complex and heterogeneous nature of SCLC tumors. This review explores the current treatment paradigm of SCLC, recent advances in immunotherapy, challenges in identifying predictive biomarkers, and potential future directions in SCLC treatment research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Pasi A. Janne, Christina Baik, Wu-Chou Su, Melissa L. Johnson, Hidetoshi Hayashi, Makoto Nishio, Dong-Wan Kim, Marianna Koczywas, Kathryn A. Gold, Conor E. Steuer, Haruyasu Murakami, James Chih-Hsin Yang, Sang-We Kim, Michele Vigliotti, Rong Shi, Zhenhao Qi, Yang Qiu, Lihui Zhao, David Sternberg, Channing Yu, Helena A. Yu
Summary: HER3-DXd shows clinical activity in EGFR TKI-resistant lung cancer, regardless of resistance mechanisms, providing a new approach to treat drug-resistant cancers.
Article
Chemistry, Medicinal
Chaofan Wang, Xiaoyun Lu
Summary: MET is a promising drug target for the treatment of MET-dependent diseases, especially NSCLC. Small molecule MET inhibitors with three types of binding modes have been developed. This review provides an overview of MET's structural features, activation mechanism, dysregulation pathway, and the development strategies of MET inhibitors, as well as the acquired resistance mechanisms. These insights will accelerate the discovery of new generation MET inhibitors to overcome clinical acquired resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Jiashuai Zhang, Zhuoxin (Zora) Zhou, Kai Chen, Seulhee Kim, Irene Soohyun Cho, Tanvi Varadkar, Hailey Baker, Ju Hwan Cho, Lufang Zhou, Xiaoguang (Margaret) Liu
Summary: The study found that anti-CD276 ADC could be a promising candidate for NSCLC treatment, showing high surface binding and tumor-specific targeting, and demonstrating good anti-tumor efficacy in models.
Article
Oncology
Yi Zhang, Silvia K. Tacheva-Grigorova, Janette Sutton, Zea Melton, Yvonne S. L. Mak, Cecilia Lay, Bryan A. Smith, Tao Sai, Thomas Van Blarcom, Barbra J. Sasu, Siler H. Panowski
Summary: The purpose of this study was to explore the role of DLL3 in SCLC and evaluate the safety and efficacy of DLL3 CAR T cells. The results showed that DLL3 CAR T cells had a strong anti-tumor effect and no significant tissue damage was observed in the brain and pituitary. Therefore, this study provides a basis for further evaluation of the potential role of DLL3 CAR T cells in the treatment of SCLC.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
S. Heynemann, H. Yu, L. Churilov, G. Rivalland, K. Asadi, R. Mosher, F. Hirsch, C. Rivard, P. Mitchell
Summary: A retrospective analysis of NaPi2b expression among resected non-small cell lung cancer specimens revealed high expression in 34.5% of cases overall, with adenocarcinoma cases showing 65.9% high expression. High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, TTF1 positivity, and improved overall survival. These findings suggest the potential of NaPi2b as a target for delivery of cytotoxic agents in lung adenocarcinoma patients.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Miki Yamaguchi, Sachie Hirai, Masashi Idogawa, Hiroaki Uchida, Yuji Sakuma
Summary: Although MET tyrosine kinase inhibitors (TKIs) are effective against non-small cell lung carcinoma (NSCLC) with MET exon 14 skipping mutations (MET delta ex14), resistance can occur. This study found that Hs-746 T cells with MET delta ex14 plus amplification exhibited primary resistance to MET TKIs. Additionally, a positive correlation was observed between MET and anthrax toxin receptor 2 (ANTXR2) mRNA expression in NSCLC cell lines. An antibody-drug conjugate (ADC) targeting ANTXR2 showed potential in inducing apoptosis in Hs-746 T cells. These findings suggest that targeting ANTXR2 with an ADC could be an effective therapeutic option for MET delta ex14-positive NSCLC.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Oncology
Htoo Zarni Oo, Zoltan Lohinai, Nastaran Khazamipour, Joey Lo, Gunjan Kumar, Jessica Pihl, Hans Adomat, Noushin Nabavi, Hakhamanesh Behmanesh, Beibei Zhai, Robert Dagil, Swati Choudhary, Tobias Gustavsson, Thomas M. Clausen, Jeffrey D. Esko, Jeffrey W. Allen, Michael A. Thompson, Nhan L. Tran, Judit Moldvay, Balazs Dome, Ali Salanti, Nader Al-Nakouzi, Glen J. Weiss, Mads Daugaard
Summary: Targeting oncofetal chondroitin sulfate (CS) chains can serve as a prognostic and therapeutic strategy for non-small cell lung cancer (NSCLC), with high expression associated with poorer outcomes. Both clinical and preclinical studies demonstrate the potential of oncofetal CS as a actionable prognostic marker and therapeutic target in NSCLC.
Review
Oncology
Saurav Verma, Daniel Breadner, Jacques Raphael
Summary: Antibody-Drug conjugates (ADCs) are a promising class of drugs that target specific cancers, delivering cytotoxic agents to tumor cells and improving therapeutic outcomes. In non-small cell lung cancer (NSCLC), several ADCs have been approved and many more are under development. These drugs, such as TROP2 targeted ADCs, provide potential options for therapy and improve outcomes for NSCLC patients. This comprehensive review discusses the recent evidence, efficacy, safety, and challenges of newer ADC candidates in NSCLC.
Review
Oncology
Elena Michaels, Christine M. Bestvina
Summary: The MET pathway can be activated by various mechanisms in NSCLC, including mutations and amplifications. Detection methods for MET alterations include RNA-based NGS and FISH. Newer selective MET TKIs have shown improved efficacy, and MET amplification is a common resistance mechanism to EGFR inhibition.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Saiama N. Waqar, Mary W. Redman, Susanne M. Arnold, Fred R. Hirsch, Philip C. Mack, Lawrence H. Schwartz, David R. Gandara, Thomas E. Stinchcombe, Natasha B. Leighl, Suresh S. Ramalingam, Saloni H. Tanna, Ryan S. Raddin, Katherine Minichiello, Jeffrey D. Bradley, Karen Kelly, Roy S. Herbst, Vassiliki A. Papadimitrakopoulou
Summary: Lung-MAP S1400K evaluated telisotuzumab vedotin in patients with previously treated c-MET-positive squamous cell carcinoma, but failed to meet the pre-specified response criteria. Pneumonitis was an unanticipated toxicity observed, leading to the closure of the trial due to lack of efficacy.
CLINICAL LUNG CANCER
(2021)
Review
Oncology
Mandy Sakamoto, Tejas Patil
Summary: Targeting the MET pathway is an important approach in the treatment of advanced NSCLC, as it plays a role in both primary oncogenesis and acquired resistance. However, the various mechanisms of MET pathway activation can complicate diagnosis and treatment. Recent developments in MET-directed therapies show promising results. This review summarizes the biology, mechanisms, diagnostic challenges, importance in acquired resistance, and novel treatment strategies of MET in advanced NSCLC.
Article
Plant Sciences
Rui Wang, Zhiyin Deng, Zhiming Zhu, Juanjuan Wang, Xiaobing Yang, Mengfei Xu, Xi Wang, Qing Tang, Qichun Zhou, Xinliang Wan, Wanyin Wu, Sumei Wang
Summary: Kaempferol inhibits non-small cell lung cancer (NSCLC) cell proliferation and promotes autophagy-induced cell death. It inhibits Met protein and mRNA expression, as well as the PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism of kaempferol in inhibiting NSCLC through autophagy regulation of the Met and PI3K/AKT/mTOR signaling pathway.
