Article
Oncology
Kota Ishioka, Hiroyuki Yasuda, Junko Hamamoto, Hideki Terai, Katsura Emoto, Tae-Jung Kim, Shigemichi Hirose, Takashi Kamatani, Sachiyo Mimaki, Daisuke Arai, Keiko Ohgino, Tetsuo Tani, Keita Masuzawa, Tadashi Manabe, Taro Shinozaki, Akifumi Mitsuishi, Toshiki Ebisudani, Takahiro Fukushima, Mari Ozaki, Shinnosuke Ikemura, Ichiro Kawada, Katsuhiko Naoki, Morio Nakamura, Takashi Ohtsuka, Hisao Asamura, Katsuya Tsuchihara, Yuichiro Hayashi, Ahmed E. Hegab, Susumu S. Kobayashi, Takashi Kohno, Hideo Watanabe, David M. Ornitz, Tomoko Betsuyaku, Kenzo Soejima, Koichi Fukunaga
Summary: In this study, FGF9 was found to play a crucial role in the transdifferentiation of lung adenocarcinoma to small cell lung cancer. The upregulation of FGF9 was confirmed to induce neuroendocrine differentiation in established human lung adenocarcinoma cells, providing direct evidence for FGF9-mediated SCLC transdifferentiation and proposing the FGF9-FGFR axis as a therapeutic target for transdifferentiated SCLC.
Article
Oncology
Kamdeo Kumar Pramanik, Rajakishore Mishra
Summary: This study found that overexpression and activation of MMP-2 are associated with invasion and metastasis of oral squamous cell carcinoma (OSCC). Treatment with MEK inhibitor and ECGC can reduce MMP-2 activity and may be used as a therapeutic strategy to control invasive OSCC.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Cell Biology
HongBo Su, GuanZhi Fan, Jin Huang, XueShan Qiu
Summary: NSCLC is a common type of cancer that leads to cancer-related deaths. The molecular mechanisms underlying NSCLC development are still unclear. This study reveals the potential role of the HOXC-AS3/YBX1/HOXC8 axis in NSCLC and suggests it as a potential biomarker for diagnosis and therapeutic target.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Xiao-Wei Zhang, Lin Li, Wen-Qian Hu, Ming-Ning Hu, Yan Tao, Hui Hu, Xiao-Kang Miao, Wen-Le Yang, Qiong Zhu, Ling-Yun Mou
Summary: This study reveals that G protein-coupled receptor neurokinin-1 (NK1R) is significantly upregulated in lung cancer samples and is associated with advanced clinical stages and poor prognosis. NK1R co-expresses with epidermal growth factor receptor (EGFR) and interacts with it in tumor cells. Activation of NK1R promotes lung cancer cell proliferation and migration through EGFR signaling pathways. Inhibition of NK1R suppresses cell proliferation and migration, and knockdown of NK1R slows down tumor growth. The presence of a selective NK1R antagonist enhances the sensitivity of lung cancer cells to specific drugs.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Jin-Dong Li, Cheng-Yan Jin, Yan Zhang, Hang Guo, Guang-Lei Zhang, Chun-Guang Wang
Summary: This case report describes a patient with lung cancer who experienced histopathological transformation from squamous-cell carcinoma to large cell neuroendocrine carcinoma with a small fraction of small cell carcinoma.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Yusuke Kimishima, Tomofumi Misaka, Tetsuro Yokokawa, Kento Wada, Koki Ueda, Koichi Sugimoto, Keiji Minakawa, Kazuhiko Nakazato, Takafumi Ishida, Motohiko Oshima, Shuhei Koide, Kotaro Shide, Kazuya Shimoda, Atsushi Iwama, Kazuhiko Ikeda, Yasuchika Takeishi
Summary: The study demonstrates that clonal hematopoiesis with JAK2V617F exacerbates PH by promoting the accumulation of neutrophils in pulmonary arterial regions, ultimately leading to pulmonary arterial remodeling and increased disease severity.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Han Wang, Yi-Jia Shen, Xiu-Juan Li, Jun Xia, Li Sun, Yehao Xu, Yu Ma, Dai Li, Yuan-Chang Xiong
Summary: Paclitaxel-induced neuropathic pain is associated with upregulation of MMP-2, which is related to reduced methylation level of its promoter. The study reveals that DNMT3b SUMOylation plays a crucial role in mediating MMP-2 upregulation and development of neuropathic pain, providing potential therapeutic targets for CIPN.
NEUROCHEMICAL RESEARCH
(2021)
Article
Oncology
Jian Feng, Huiling Ouyang, Jing Wang, Deshen Pan, Luoyan Sheng, Chaoliang Xu, Weihong Lin, Dingzhong Hu, Cheng Chang, Deshui Jia
Summary: This study found that MPZL1 gene is upregulated in non-small cell lung cancer (NSCLC) and high expression is associated with unfavorable prognosis. Ectopic overexpression of MPZL1 promotes migratory ability of lung cancer cells, while knockdown of MPZL1 impairs migration. By analyzing gene expression, COL11A1 was identified as a potential effector gene positively regulated by MPZL1 and correlated with poor prognosis in NSCLC patients.
Article
Biochemistry & Molecular Biology
Qun Wang, Jing Wu, Hua Wei, Hui Huang, Ying Huang, Hongyan Fang, Xiaojun Gong, Jun Sun, Yujuan Wu, Changjiang Lei, Jinming Yu, Desheng Hu
Summary: Increased stemness and drug resistance in lung cancer are linked to upregulation of JARID2, which also correlates with poor clinical outcomes. Targeting JARID2 may provide a promising approach to overcome drug resistance in NSCLC.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Immunology
Shuo Kong, Tao-xiang Chen, Xiang-lei Jia, Xue-lei Cheng, Meng-liu Zeng, Jing-yi Liang, Xiao-hua He, Jun Yin, Song Han, Wan-hong Liu, Yuan-teng Fan, Ting Zhou, Yu-min Liu, Bi-wen Peng
Summary: NFIA upregulation in the hippocampal region is astrocyte-specific and primarily promotes detrimental actions of reactive astrocyte. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Oncology
Yingjing Wang, Lu Shen, Geng Li, Jiayi Chen, Rong Ge
Summary: This study found that XIAP is significantly upregulated in lung adenocarcinoma with brain metastasis and is significantly associated with tumor grade and metastasis. In addition, XIAP is closely correlated with multiple immune cells. These findings have important implications for the prediction and clinical treatment of lung adenocarcinoma with brain metastasis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Virology
Hsiang-Chi Huang, Shih-Han Wang, Guo-Chen Fang, Wen-Cheng Chou, Chun-Che Liao, Cheng-Pu Sun, Jia-Tsrong Jan, Hsiu-Hua Ma, Hui-Ying Ko, Yi-An Ko, Ming-Tsai Chiang, Jian-Jong Liang, Chun-Tse Kuo, Te-An Lee, Diego Morales-Scheihing, Chen-Yang Shen, Shih-Yu Chen, Louise D. McCullough, Lu Cui, Gerlinde Wernig, Mi-Hua Tao, Yi-Ling Lin, Yao-Ming Chang, Shu-Ping Wang, Yun-Ju Lai, Chia-Wei Li
Summary: Patients with severe COVID-19 often experience lymphopenia, and this study aims to understand how SARS-CoV-2 induces this condition. The researchers analyzed the transcriptomic and epigenomic changes in infected cells and found that the NF-κB and IRF1-PD-L1 pathways play a role in viral infection and COVID-19 severity. They also observed higher expression of PD-L1 in Omicron-infected cells compared to SARS-CoV-2-infected cells. Blocking PD-L1 in virally-infected mice showed promising results in recovering lymphocyte counts and reducing inflammatory cytokine levels. Targeting the NF-κB and IRF1-PD-L1 axis could be an alternative strategy to mitigate the severity of COVID-19.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Caimei Wang, Yiyuan Wang, Congrong Liu, Xiaoyu Meng, Zhongxia Hang
Summary: This study reveals the important role of KNTC1 in the development of cervical cancer and identifies the mechanism by which KNTC1 promotes cervical cancer through MMP9 and MMP2-mediated reduction in tumor cell invasion and migration abilities.
Article
Oncology
Lu Liu, Chunsun Li, Zhen Wu, Yanqin Li, Hang Yu, Tao Li, Yueming Wang, Wei Zhao, Liangan Chen
Summary: LCMR1 is highly expressed in large cell lung cancer and its high expression is associated with poor prognosis. Blocking LCMR1 reduces proliferation and metastasis of cancer cells by inhibiting the transcription of HLA genes.
Article
Biochemistry & Molecular Biology
Yu-Hsiang Chang, Yuan-Li Huang, Hsiao-Chi Tsai, An-Chen Chang, Chih-Yuan Ko, Yi-Chin Fong, Chih-Hsin Tang
Summary: This study aims to investigate the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The results demonstrate a positive correlation between CCL2 or MMP-3 levels and osteosarcoma metastasis, and stimulation of osteosarcoma cells with CCL2 enhances migration and invasion abilities. Additionally, CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis.
Article
Oncology
Paul K. Paik, Pang-Dian Fan, Besnik Qeriqi, Azadeh Namakydoust, Bobby Daly, Linda Ahn, Rachel Kim, Andrew Plodkowski, Ai Ni, Jason Chang, Rachel Fanaroff, Marc Ladanyi, Elisa de Stanchina, Charles M. Rudin
Summary: Increased understanding of the mutational landscape of squamous cell lung cancers (LUSCs) has not resulted in effective targeted therapies. This study investigates the potential of TORC1/2 inhibitor TAK-228 in NSCLC models with NRF2-activating alterations and reports positive outcomes in a phase 2 clinical trial. TAK-228 shows promising single-agent activity in LUSC patients with NRF2 activation and highlights the importance of targeting metabolism in NSCLC.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Review
Oncology
Kenta Kawasaki, Natasha Rekhtman, Alvaro Quintanal-Villalonga, Charles M. Rudin
Summary: The review provides a comprehensive overview of the current understanding of NENs in the gastrointestinal system and lung from both clinical and biological perspectives. The authors discuss the commonalities and organ-specific differences of NENs and advocate for a tissue-agnostic approach to drug development, in order to improve patient care by accelerating research across different disease entities.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Oncology
Noura J. Choudhury, Antonio Marra, Jane S. Y. Sui, Jessica Flynn, Soo-Ryum Yang, Christina J. Falcon, Pier Selenica, Adam J. Schoenfeld, Natasha Rekhtman, Daniel Gomez, Michael F. Berger, Marc Ladanyi, Maria Arcila, Charles M. Rudin, Gregory J. Riely, Mark G. Kris, Glenn Heller, Jorge S. Reis-Filho, Helena A. Yu
Summary: The study explores the potential of identifying and intervening on molecular markers associated with therapeutic resistance to improve patient outcomes in metastatic EGFR-mutant lung cancer treated with first-line osimertinib. Baseline atypical EGFR and concurrent TP53/RB1 alterations are associated with shorter progression-free survival on first-line osimertinib. Tissue-based genomic analysis allows for treatment adaptation based on identified mechanisms of resistance at the time of progression, leading to improved postprogression survival.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Charles M. Rudin, Hardev S. Pandha, Matthew Zibelman, Wallace L. Akerley, Kevin J. Harrington, Daphne Day, Andrew G. Hill, Steven J. O'Day, Timothy D. Clay, Gavin M. Wright, Ross R. Jennens, David E. Gerber, Jonathan E. Rosenberg, Christy Ralph, David C. Campbell, Brendan D. Curti, Jaime R. Merchan, Yixin Ren, Emmett Schmidt, Lisa Guttman, Sumati Gupta
Summary: This study evaluated the efficacy and safety of V937 combined with pembrolizumab in patients with advanced solid tumors. The results showed that the combination therapy had a manageable safety profile, but did not achieve greater efficacy than pembrolizumab monotherapy in non-small cell lung cancer and urothelial cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Editorial Material
Oncology
Salomon Tendler, Charles M. Rudin
JOURNAL OF CLINICAL ONCOLOGY
(2023)
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
Oncology
Charles M. Rudin, David Balli, W. Victoria Lai, Allison L. Richards, Evelyn Nguyen, Jacklynn Egger, Noura J. Choudhury, Triparna Sen, Andrew Chow, John T. Poirier, William J. Geese, Matthew D. Hellmann, Ann Forslund
Summary: A study found that antigen presentation machinery signature and infiltrating CD8 T cells were correlated with survival in SCLC patients treated with nivolumab, suggesting their potential as biomarkers for predicting immunotherapy efficacy. The study also identified the association between durable benefit from immunotherapy and antigen processing and presentation.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Immunology
Ariella Glasner, Samuel A. Rose, Roshan Sharma, Herman Gudjonson, Tinyi Chu, Jesse A. Green, Sham Rampersaud, Izabella K. Valdez, Emma S. Andretta, Bahawar S. Dhillon, Michail Schizas, Stanislav Dikiy, Alejandra Mendoza, Wei Hu, Zhong-Min Wang, Ojasvi Chaudhary, Tianhao Xu, Linas Mazutis, Gabrielle Rizzuto, Alvaro Quintanal-Villalonga, Parvathy Manoj, Elisa de Stanchina, Charles M. Rudin, Dana Pe'er, Alexander Y. Rudensky
Summary: Traditional roles of regulatory T (T-reg) cells as suppressors of antigen presenting cells and effector T cells have expanded to include tissue maintenance functions, suggesting a broader regulatory role than previously thought. In lung cancer and injury-induced inflammation, T-reg cell depletion led to changes in gene expression in fibroblasts, endothelial and myeloid cells, involving VEGF and CCR2 signaling. Combined T-reg cell depletion and short-term VEGF blockade showed improved control of PD-1 blockade-resistant lung adenocarcinoma progression, highlighting the potential of combination therapies for solid organ cancers.
Article
Biochemistry & Molecular Biology
Qi Xu, Jeanne Kowalski
Summary: Alternate forms of DNA, such as Z-DNA, G-quadruplex, and triplex, have shown potential roles in cancer development. Non-B DNA-forming sequences have been found to induce genetic instability in human cancer genomes, implicating their involvement in cancer and other genetic diseases. However, existing non-B prediction tools and databases lack the capability to analyze and visualize non-B data in a cancer context. In this study, we present NBBC, a non-B DNA burden explorer in cancer, which provides analysis and visualization for non-B DNA forming motifs. We introduce the concept of 'non-B burden' as a metric to summarize the prevalence of non-B DNA motifs at different levels. With the non-B burden metric, we develop two analysis modules within a cancer context, aiming to explore both gene- and motif-level heterogeneity of non-B DNA. NBBC is designed as a novel analysis and visualization platform guided by non-B burden as a marker.
NUCLEIC ACIDS RESEARCH
(2023)
Editorial Material
Oncology
Charles M. Rudin
Article
Oncology
Subhamoy Chakraborty, Charles Coleman, Parvathy Manoj, Deniz Demircioglu, Nisargbhai Shah, Elisa de Stanchina, Charles M. Rudin, Dan Hasson, Triparna Sen
Summary: Lurbinectedin significantly reduces cell viability in most SCLC models, with the best response observed in POU2F3-driven SCLC cells. We also found that lurbinectedin, either as a single agent or in combination with osimertinib, shows an appreciable antitumor response in EGFR-mutant lung adenocarcinoma models with histologic transformation to SCLC. Transcriptomic analysis revealed the induction of apoptosis, repression of epithelial-mesenchymal transition, and modulation of PI3K/AKT, NOTCH signaling associated with lurbinectedin response in both de novo and transformed SCLC models.
CLINICAL CANCER RESEARCH
(2023)
Article
Genetics & Heredity
Jaspreet Kaur, Darshan S. Chandrashekar, Zsuzsanna Varga, Bettina Sobottka, Emiel Janssen, Khanjan Gandhi, Jeanne Kowalski, Umay Kiraz, Sooryanarayana Varambally, Ritu Aneja
Summary: This study investigated the genetic profile of triple-negative breast cancer (TNBC) through whole-exome sequencing (WES) analysis. The results showed similar mutational features between primary tumors and recurrent tumors, suggesting that genomic features may be retained during local recurrence.
Article
Multidisciplinary Sciences
Qi Xu, Jeanne Kowalski
Summary: Molecular profiling reports (MPRs) are crucial for cancer treatment decisions, but synthesizing the complex information contained within them is challenging. Xu and Kowalski developed myCMIE, a web application that provides a patient-centric information system for exchanging molecular profiles and facilitating context-informed treatment options. myCMIE uses interactive digital-twin communities and visualizations to promote discussions among diverse stakeholders in healthcare.
Article
Oncology
Joy A. Pai, Matthew D. Hellmann, Jennifer L. Sauter, Marissa Mattar, Hira Rizvi, Hyung Jun Woo, Nisargbhai Shah, Evelyn M. Nguyen, Fathema Z. Uddin, Alvaro Quintanal-Villalonga, Joseph M. Chan, Parvathy Manoj, Viola Allaj, Marina K. Baine, Umesh K. Bhanot, Mala Jain, Irina Linkov, Fanli Meng, David Brown, Jamie E. Chaft, Andrew J. Plodkowski, Mathieu Gigoux, Helen H. Won, Triparna Sen, Daniel K. Wells, Mark T. A. Donoghue, Elisa de Stanchina, Jedd D. Wolchok, Brian Loomis, Taha Merghoub, Charles M. Rudin, Andrew Chow, Ansuman T. Satpathy
Summary: Paired scRNA/TCR-seq analysis of T cells from NSCLC patients after ICB reveals clonally linked TFH and tumor-specific CD8+ T cells in tumor draining LNs. Exhausted CD8+ T cells, Treg, and TFH cells show progressive exhaustion trajectories with proximity to the tumor microenvironment. Longitudinal tracking demonstrates the persistence of tumor-specific T cell clones in peripheral blood for years after ICB therapy.
Article
Medicine, Research & Experimental
Janneke E. Jaspers, Jonathan F. Khan, William D. Godfrey, Andrea Lopez, Metamia Ciampricotti, Charles M. Rudin, Renier J. Brentjens
Summary: This study developed a chimeric antigen receptor (CAR) against DLL3 and demonstrated its antitumor efficacy in xenograft and murine SCLC models. CAR T cell expression of IL-18 enhanced the potency of DLL3-targeting CAR T cell therapy and increased the activation of CAR T cells and tumor-infiltrating lymphocytes. Human IL-18-secreting anti-DLL3 CAR T cells showed durable responses in multiple SCLC models, and this effect could be further enhanced with anti-PD-1 blockade.
JOURNAL OF CLINICAL INVESTIGATION
(2023)