Review
Oncology
Weichang Yang, Wenjun Wang, Zhouhua Li, Juan Wu, Xiaotian Huang, Jinbo Li, Xinyi Zhang, Xiaoqun Ye
Summary: Small cell lung cancer is a highly invasive and aggressive type of lung cancer with limited treatment options. Delta-like ligand 3 (DLL3) is overexpressed on the surface of SCLC cells and is considered a potential target for SCLC treatment. Several drug trials targeting DLL3 are currently underway.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Article
Medicine, General & Internal
Christiane Kuempers, Tobias Jagomast, Rosemarie Krupar, Finn-Ole Paulsen, Carsten Heidel, Julika Ribbat-Idel, Christian Idel, Bruno Maerkl, Martin Anlauf, Sabina Berezowska, Markus Tiemann, Hans Boesmueller, Falko Fend, Barbara Kalsdorf, Sabine Bohnet, Eva Dreyer, Verena Sailer, Jutta Kirfel, Sven Perner
Summary: Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, is being developed for SCLC. DLL3 expression was found in the majority of chemonaive and chemorelapsed SCLC samples, with variations in expression levels. Although DLL3 expression did not correlate significantly with clinicopathological data, high DLL3 expression in chemorelapsed samples showed a trend towards better prognosis.
FRONTIERS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Maximilian W. Schenk, Sam Humphrey, A. S. Md Mukarram Hossain, Mitchell Revill, Sarah Pearsall, Alice Lallo, Stewart Brown, Samuel Bratt, Melanie Galvin, Tine Descamps, Cong Zhou, Simon P. Pearce, Lynsey Priest, Michelle Greenhalgh, Anshuman Chaturvedi, Alastair Kerr, Fiona Blackhall, Caroline Dive, Kristopher K. Frese
Summary: In small cell lung cancer, acquired resistance to standard platinum-etoposide chemotherapy often occurs, with Notch and nitric oxide pathways playing a role in mediating this resistance. Upregulation of soluble guanylate cyclase in residual tumor cells is associated with chemoresistance, highlighting this pathway as a potential target for treating relapsed SCLC.
NATURE COMMUNICATIONS
(2021)
Article
Developmental Biology
Seoyeon Jang, Jeon Lee, Jeremy Mathews, Holly Ruess, Anna O. Williford, Prashanth Rangan, Esther Betran, Michael Buszczak
Summary: The study suggests that ribosome heterogeneity plays a vital role in mRNA translation in different cell types and conditions. Deleting RpS5b in fruit flies leads to female sterility with developmental issues in egg chambers, disrupted vitellogenesis, and hyperplasia in posterior follicle cells. Loss of RpS5b also results in increased rRNA transcription and protein synthesis, causing defects in microtubules and mislocalization of important proteins in the Notch pathway.
Article
Oncology
Greta Ali, Iose Di Stefano, Anello Marcello Poma, Stefano Ricci, Agnese Proietti, Federico Davini, Marco Lucchi, Franca Melfi, Gabriella Fontanini
Summary: Research showed high prevalence of DLL3 expression in high-grade lung NET patients, associated with aggressive clinicopathological features, suggesting its potential as a useful biomarker for target therapy in high-grade tumors.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Charles M. M. Rudin, Martin Reck, Melissa L. L. Johnson, Fiona Blackhall, Christine L. L. Hann, James Chih-Hsin Yang, Julie M. M. Bailis, Gwyn Bebb, Amanda Goldrick, John Umejiego, Luis Paz-Ares
Summary: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine carcinoma with limited treatment options. DLL3, a Notch inhibitory ligand, is overexpressed on SCLC cells, making it an attractive therapeutic target. This article discusses the clinical experience with a DLL3-targeting antibody-drug conjugate called Rova-T, as well as other DLL3-targeting agents currently in development, including T-cell engager molecules and CAR T-cell therapy. The challenges and opportunities for DLL3-targeting therapies, such as using DLL3 as a biomarker and exploring combinatorial approaches, are also discussed.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Cell Biology
Jerome Levallet, Tiphaine Biojout, Celine Bazille, Manon Douyere, Fatemeh Dubois, Dimitri Leite Ferreira, Jasmine Taylor, Sylvain Teulier, Jerome Toutain, Nicolas Elie, Myriam Bernaudin, Samuel Valable, Emmanuel Bergot, Guenaelle Levallet
Summary: The over-activation of NDR2 kinase under hypoxia conditions promotes brain metastasis formation in NSCLC. NDR2 expression serves as a reliable indicator for predicting the risk of metastasis in NSCLC patients.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Qingzhe Wu, Jingxin Guo, Yuning Liu, Qi Zheng, Xiaoling Li, Chuanqiang Wu, Dong Fang, Xin Chen, Liang Ma, Pinglong Xu, Xiaofang Xu, Cheng Liao, Ming Wu, Li Shen, Hai Song
Summary: The study reveals that YAP plays critical roles in the establishment of intratumoral heterogeneity in SCLC, affecting the development of SCLC by promoting fate conversion from NE to Non-NE tumor cells and enhancing chemoresistance.
Article
Multidisciplinary Sciences
Jun W. Kim, Julie H. Ko, Julien Sage
Summary: This study investigates the role of tumor heterogeneity in small-cell lung cancer (SCLC) and identifies DLL3 as a biomarker of neuroendocrine state and a regulator of cell-cell interactions in SCLC.
Article
Cell Biology
Meng Chen, Li-Xin Sun, Long Yu, Jun Liu, Li-Chao Sun, Zhi-Hua Yang, Xiong Shu, Yu-Liang Ran
Summary: MYH9 regulates the stem cell-like characteristics of LCCs by affecting the mTOR signaling pathway, and its high expression in lung cancer is associated with poor clinical prognosis in NSCLC patients.
CELL DEATH DISCOVERY
(2021)
Article
Oncology
Kathryn M. Tully, Salomon Tendler, Lukas M. Carter, Sai Kiran Sharma, Zachary Samuels, Komal Mandleywala, Joshua A. Korsen, Avelyn Mae Delos Reyes, Alessandra Piersigilli, William D. Travis, Triparna Sen, Nagavarakishore Pillarsetty, John T. Poirier, Charles M. Rudin, Jason S. Lewis
Summary: In the treatment of small cell lung cancer, [Lu-177]Lu-DTPA-CHX-A-SC16 showed good targeting and antitumor efficacy, with mild and transient toxicity.
CLINICAL CANCER RESEARCH
(2022)
Review
Medicine, Research & Experimental
Huan Zhang, Yunkai Yang, Xuchang Li, Xun Yuan, Qian Chu
Summary: Small cell lung cancer (SCLC) is a highly aggressive and poorly differentiated cancer with limited treatment options. Notch signaling, specifically the Notch ligand DLL3, has been identified as a potential therapeutic target in SCLC. This article summarizes the functional relevance of Notch signaling in SCLC, discusses targeted therapy and ongoing clinical trials, and explores the potential synergy with immune checkpoint inhibitors (ICIs).
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Yingying Wang, Minli Wei, Min Su, Zhiyuan Du, Jiaxi Dong, Yu Zhang, Yingdi Wu, Xiaopeng Li, Ling Su, Xiangguo Liu
Summary: DIRAS3, a candidate tumor suppressor protein, inhibits the migration of NSCLC cells by promoting the polyubiquitination and degradation of RAC1 through the interaction with RNF19B. The DIRAS3-RNF19B-RAC1 axis is associated with the malignant progression of NSCLC.
Article
Multidisciplinary Sciences
Xiao Qi, Zihao Li, Jinrui Zhang, Hongru Li, Guangxin Zhang, Meng Li, Baofeng Li, Yilin Fu, Mingjun Cai, Hongda Wang, Ti Tong, Jing Gao
Summary: CDCP1 is a transmembrane protein involved in important biological processes and is upregulated in human solid malignancies. However, its spatial distribution and variation at the molecular level are unclear. This study analyzed CDCP1 expression and prognostic implications in lung cancer, and used super-resolution microscopy to reveal its spatial organization. The findings showed significant differences in CDCP1 clustering characteristics between cancer and normal cells, highlighting its potential as a target for lung cancer drugs.
Article
Biochemistry & Molecular Biology
Huan Ma, Siyu Jiang, Yinan Yuan, Ji Li, Yizhuo Li, Yanping Lv, Tengjiao Du, Jingqian Guan, Xizi Jiang, Lei Tian, Qianqian Zheng, Lianhe Yang, Qingchang Li
Summary: RUNX1, a member of the RUNX family, is involved in the regulation of non-small cell lung cancer. It promotes cell proliferation and migration via the mTOR pathway and may serve as a potential therapeutic target for NSCLC.
Article
Oncology
Hirofumi Takahashi, Jun Sakakibara-Konishi, Megumi Furuta, Tetsuaki Shoji, Kosuke Tsuji, Daisuke Morinaga, Eiki Kikuchi, Junko Kikuchi, Takuro Noguchi, Kanako C. Hatanaka, Yutaka Hatanaka, Naofumi Shinagawa, Satoshi Konno
Summary: Notch pathway may be involved in the development of osimertinib resistance in EGFR-mutated NSCLC patients, and the combination of Notch inhibitors and osimertinib may be a potential therapeutic approach.