Article
Oncology
Tinglei Huang, Biying Chen, Feng Wang, Weiyang Cai, Xinxin Wang, Bo Huang, Feng Liu, Bin Jiang, Yanjie Zhang
Summary: This study found that Rab1A overexpression in non-small cell lung cancer is significantly correlated with aggressive tumor growth and metastasis by activating the JAK1/STAT6 signaling pathway. Additionally, Rab1A levels also impact sensitivity to JAK1 inhibitors, potentially enhancing the efficacy of JAK1-targeted cancer therapy.
Article
Medicine, Research & Experimental
Yuan Gu, Gianni Pais, Vivien Becker, Christina Korbel, Emmanuel Ampofo, Elke Ebert, Johannes Hohneck, Nicole Ludwig, Eckart Meese, Rainer M. Bohle, Yingjun Zhao, Michael D. Menger, Matthias W. Laschke
Summary: The research demonstrates that miR-22 is highly expressed in ECs and significantly downregulated in NSCLC tissues. Endothelial miR-22 acts as an angiogenesis inhibitor by targeting sirtuin 1 and FGFR1 to inhibit ECs' angiogenic activities, thus suppressing NSCLC growth.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
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
Immunology
Aiko Hirayama, Kentaro Tanaka, Hirono Tsutsumi, Takayuki Nakanishi, Sho Yamashita, Shun Mizusaki, Yumiko Ishii, Keiichi Ota, Yasuto Yoneshima, Eiji Iwama, Isamu Okamoto
Summary: In this study, we found that PD-L1 expression in non-small cell lung cancer is regulated by IL-1 beta. The combination of IL-1 beta and IFN-gamma can synergistically increase PD-L1 expression and activate the MAPK signaling pathway. Inhibitors of MAPK signaling can block the upregulation of PD-L1 by IL-1 beta and IFN-gamma.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Arun Rajan, Jhanelle E. Gray, Siddhartha Devarakonda, Ruemu Birhiray, Borys Korchin, Erika Menius, Renee N. Donahue, Jeffrey Schlom, James L. Gulley
Summary: CV301 in combination with PD-1 inhibitors is safe and clinically active in advanced NSCLC patients, without an increased frequency or severity of immune-related adverse events.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Soon-Young Jung, Hyun Kyoung Lee, Hyungmin Kim, Seulki Kim, Jung Soo Kim, Jeong Gu Kang, Hyo-Jeong Kuh, Jong Shin Yoo, Jeong-Heon Ko, Jeong-Hwa Lee
Summary: Alterations in sialylation of terminal residues of glycoproteins have been implicated in forming tumor associated glycans. The impact of ST6GALNACIII on tumor progression remains undefined. ST6GALNACIII plays an important role in promoting A549 cell growth through quantitative regulation of TFR1 expression.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biology
Xiaolong Tang, Lizhi Cheng, Guo Li, Yong-Ming Yan, Fengting Su, Dan-Ling Huang, Shuping Zhang, Zuojun Liu, Minxian Qian, Ji Li, Yong-Xian Cheng, Baohua Liu
Summary: The small molecule compound D6 demonstrates promising efficacy in treating EGFR-TKI resistant NSCLC by targeting the protein-protein interaction between HSP90 and T790M-EGFR, offering a potential alternative strategy to overcome drug resistance.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Jessica M. Konen, B. Leticia Rodriguez, Haoyi Wu, Jared J. Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I. Wistuba, Jianjun Zhang, Don L. Gibbons
Summary: Non-small cell lung cancers with KRAS and TP53 mutations show partial response to anti-PD-(L)1 treatment, but most patients do not experience durable clinical benefit. In this study, mouse lung cancer models with intrinsic resistance to anti-PD-1 were developed, and differential gene expression was analyzed to identify novel resistance mechanisms. It was found that the enzyme autotaxin (ATX) and the metabolite lysophosphatidic acid (LPA) were upregulated in resistant tumors and negatively correlated with CD8+ T cell infiltration. Inhibition of ATX or its downstream receptor LPAR5, in combination with anti-PD-1, effectively restored the anti-tumor immune response and controlled tumor growth. These findings suggest that the ATX/LPA axis is an immunosuppressive pathway that hampers the response to immune checkpoint blockade in lung cancer.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Cell Biology
Zhe Liu, Liang Ma, Yiming Sun, Wenying Yu, Xue Wang
Summary: The study demonstrated that the STAT3/ZEB1 axis is critical in gefitinib resistance in lung cancer, and a new potential therapeutic strategy targeting STAT3 has been identified with the inhibitor LL1. LL1 was shown to sensitize resistant cells to gefitinib by depleting STAT3 activity and blocking its signaling pathways, with little observed toxicity in animal models, indicating it could be a chemotherapeutic adjuvant for gefitinib resistance in NSCLC.
CELL DEATH & DISEASE
(2021)
Article
Medicine, General & Internal
Charles M. Rudin, Elisabeth Brambilla, Corinne Faivre-Finn, Julien Sage
Summary: Small-cell lung cancer is a type of lung cancer characterized by high proliferative rate, early metastasis, and poor prognosis, strongly associated with tobacco carcinogens. Most patients are diagnosed with metastatic disease, with only a small fraction having potentially curative earlier-stage disease. Genomic profiling reveals extensive chromosomal rearrangements and high mutation burden in SCLC, often involving inactivation of TP53 and RB1 tumor suppressor genes.
NATURE REVIEWS DISEASE PRIMERS
(2021)
Article
Cell Biology
Danielle S. Potter, Ruochen Du, Patrick Bhola, Raphael Bueno, Anthony Letai
Summary: By utilizing dynamic BH3 profiling (DBP) to measure drug-induced mitochondrial apoptotic priming, it is possible to identify drugs that render tumors more sensitive to conventional chemotherapy and to rationally construct combination therapies. Research has shown that targeted agents that increase priming of NSCLC tumor cells can enhance sensitivity to chemotherapy both in vitro and in vivo.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Giuseppe Giaccone, Yongfeng He
Summary: Lung cancer is the leading cause of cancer related death, with two major histological subtypes, NSCLC and SCLC. Transformation from NSCLC to SCLC can cause treatment resistance, potentially due to therapy-induced changes or clonal selection. This article discusses the potential mechanisms, cell of origin, and genomic alterations in both de novo and transformed SCLC, as well as treatment options including chemotherapy, radiotherapy, TKIs, immunotherapy, and antiangiogenic agents.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Bin Wu, Ning Chang, Hangtian Xi, Jie Xiong, Ying Zhou, Yingtong Wu, Shuo Wu, Ning Wang, Hongyu Yi, Yun Song, Lihua Chen, Jian Zhang
Summary: PHB2 facilitates tumorigenesis in non-small cell lung cancer by interacting with and stabilizing RACK1 to activate downstream tumor-promoting effectors. The crosstalk between PHB2 and RACK1 provides a potential therapeutic target for novel strategies in treating NSCLC.
Article
Oncology
Jiaxin Liu, Lingyun Wei, Nan Hu, Dong Wang, Juan Ni, Sha Zhang, Hongbing Liu, Tangfeng Lv, Jie Yin, Mingxiang Ye, Yong Song
Summary: This study reveals the critical role of FBW7 in determining the stability of PD-1 protein and demonstrates that targeting FBW7 can enhance anti-tumor immunity. In addition, the study found that the expression level of FBW7 can predict the clinical response to anti-PD-1 immunotherapy in NSCLC patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Genetics & Heredity
Kai-Ling Lee, Tsung-Ching Lai, Yao-Chen Wang, Pei-Chun Shih, Yi-Chieh Yang, Thomas Chang-Yao Tsao, Tu-Chen Liu, Yu-Ching Wen, Lun-Ching Chang, Shun-Fa Yang, Ming-Hsien Chien
Summary: The study explored the associations between IL-17A gene polymorphisms, EGFR mutation status, and clinicopathologic development of LUAD in a Taiwanese population. While IL-17A SNPs were not correlated with EGFR mutation risk, rs8193036 and rs8193037 were identified as potential markers for predicting clinical prognoses in LUAD patients.
Review
Pharmacology & Pharmacy
Diego Kauffmann-Guerrero, Kathrin Kahnert, Rudolf M. Huber
Summary: Non-small-cell lung cancer (NSCLC) constitutes the majority of lung cancer cases, with emerging targeted therapies providing significant progress in treating a subset of patients. ALK tyrosine kinase inhibitors have greatly improved treatment options and outcomes for ALK-positive NSCLC patients.
Article
Respiratory System
Michaela Schunk, Lien Le, Zulfiya Syunyaeva, Birgit Haberland, Susanne Taenzler, Ulrich Mansmann, Larissa Schwarzkopf, Hildegard Seidl, Sabine Streitwieser, Miriam Hofmann, Thomas Mueller, Tobias Weiss, Philipp Morawietz, Eva Annette Rehfuess, Rudolf Maria Huber, Ursula Berger, Claudia Bausewein
Summary: The Munich Breathlessness Service (MBS) was tested in the BreathEase trial for patients with chronic breathlessness in advanced disease and their carers, showing positive effects in reducing burden caused by chronic breathlessness. Further evaluation in subgroups of patients and with a longitudinal perspective is needed.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Oncology
Anna Kerpel-Fronius, Martin Tammemagi, Milena Cavic, Claudia Henschke, Long Jiang, Ella Kazerooni, Choon-Taek Lee, Luigi Ventura, Dawei Yang, Stephen Lam, Rudolf M. Huber
Summary: The feasibility and effectiveness of lung cancer screening for individuals who never smoked are uncertain due to current screening guidelines typically excluding this group. Evaluation in each country considering various factors, including risk assessment accuracy and cost-effectiveness, is necessary. Current evidence supporting widespread implementation of screening for never smokers is lacking.
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Cell Biology
Marcel Andre Schneider, Laura Heeb, Michal Mateusz Beffinger, Stanislav Pantelyushin, Michael Linecker, Lilian Roth, Kuno Lehmann, Udo Ungethum, Sebastian Kobold, Rolf Graf, Maries Van den Broek, Johannes Vom Berg, Anurag Gupta, Pierre-Alain Clavien
Summary: Peripheral serotonin has pleiotropic effects on coagulation, metabolism, tissue regeneration, and cancer growth, but its impact on the tumor microenvironment is understudied. Serotonin deficiency in mice leads to reduced tumor growth, increased CD8(+) T cell accumulation, and decreased PD-L1 expression, suggesting a role in immune response regulation. Serotonin regulates PD-L1 expression on tumor cells through serotonylation and affects tumor growth and immune response.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Melanie Schwerdtfeger, Vincenzo Desiderio, Sebastian Kobold, Tarik Regard, Silvia Zappavigna, Michele Caraglia
Summary: Research has shown that lncRNAs play roles in various physiological and pathological events, including immune system regulation and cancer; while CSCs, as a group of cancer cells with specific characteristics, are crucial for tumor growth and progression in conjunction with the cancer microenvironment, genetics, and epigenetics.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Oncology
Rudolf M. Huber, Milena Cavic, Anna Kerpel-Fronius, Lucia Viola, John Field, Long Jiang, Ella A. Kazerooni, Coenraad F. N. Koegelenberg, Anant Mohan, Ricardo Sales Dos Santos, Luigi Ventura, Murry Wynes, Dawei Yang, Javier Zulueta, Choon-Taek Lee, Martin C. Tammemagi, Claudia Henschke, Stephen Lam
Summary: This report discusses the importance of global implementation of lung cancer screening and the impact of respiratory infections such as COVID-19 on screening. It highlights the risk of false positive results due to respiratory infections and provides guidance and recommendations for these situations, while also calling for further research and discussions.
JOURNAL OF THORACIC ONCOLOGY
(2022)
Letter
Oncology
Anna Kerpel-Fronius, Martin C. Tammemagi, Milena Cavic, Rudolf M. Huber, Dawei Yang, Javier Zulueta, Lucia Viola, Anant Mohan, Choon-Taek Lee, Milena Cavic, Heidi Schmidt, Ella Kazerooni, Ricardo Sales dos Santos, Claudia Henschke, Luigi Ventura, Long Jiang, Gabriella Sozzi, Stephen Lam, Rudolf Huber
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sophia Stock, Anna-Kristina Kluever, Stefan Endres, Sebastian Kobold
Summary: Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in treating specific hematological malignancies. However, many patients do not respond or relapse after treatment. Strategies such as combining CAR T cells with other treatments and using clinically approved compounds have been investigated to improve this therapy.
Article
Biochemistry & Molecular Biology
Kristina A. M. Arendt, Giannoula Ntaliarda, Vasileios Armenis, Danai Kati, Christin Henning, Georgia A. Giotopoulou, Mario A. A. Pepe, Laura Klotz, Anne-Sophie Lamort, Rudolf A. Hatz, Sebastian Kobold, Andrea C. Schamberger, Georgios T. Stathopoulos
Summary: KRAS-mutant tumor cells showed exclusive response to KRAS blockade in vivo by co-opting host myeloid cells through C-C-motif chemokine ligand 2 (CCL2)/interleukin-1 beta (IL-1 beta)-mediated signaling loop. In vitro cellular systems are suboptimal for anti-KRAS drug screens and IL-1 beta blockade might be suitable for therapy for KRAS-mutant cancers.
Review
Immunology
Stefanos Michaelides, Hannah Obeck, Daryna Kechur, Stefan Endres, Sebastian Kobold
Summary: Adoptive cell therapy and chimeric antigen receptor T cell therapy are potential strategies for cancer treatment, but their effectiveness in solid tumors is limited. One of the main challenges is the poor access of transferred T cells to the tumor site. Engineering T cells is being explored to improve the efficacy of adoptive cell therapy in solid tumors.
Article
Oncology
Veronika Lutz, Veronique M. Hellmund, Felix S. R. Picard, Hartmann Raifer, Teresa Ruckenbrod, Matthias Klein, Tobias Bopp, Rajkumar Savai, Peter Duewell, Corinna U. Keber, Andreas Weigert, Ho-Ryun Chung, Malte Buchholz, Andre Menke, Thomas M. Gress, Magdalena Huber, Christian Bauer
Summary: Signaling through IL18R induces exhaustion of CD8(+) T cells, characterized by expression of coinhibitory receptors and loss of effector function. This exhaustion is mediated by an NLRP3-expressing tumor microenvironment that releases IL18. These findings suggest that NLRP3-mediated IL18R signaling could be a potential target for immunotherapy in pancreatic carcinoma.
CANCER IMMUNOLOGY RESEARCH
(2023)
Review
Oncology
David Andreu-Sanz, Sebastian Kobold
Summary: While CD8(+) T cells have been the focus of most cancer immunotherapy approaches, increasing evidence indicates that CD4(+) T cells also play a crucial role in tumor elimination. These T cells can differentiate into different subsets, which have diverse effects on tumor progression depending on the cytokine milieu. This review provides an overview of the role of T helper subsets in the immune system, their implications in cancer immunology, and their applications in adoptive T-cell therapy.
Article
Cell Biology
Simon Heidegger, Florian Stritzke, Sarah Dahl, Juliane Dassler-Plenker, Laura Joachim, Dominik Buschmann, Kaiji Fan, Carolin M. Sauer, Nils Ludwig, Christof Winter, Stefan Enssle, Suqi Li, Markus Perl, Andre Goergens, Tobias Haas, Erik Thiele Orberg, Sascha Goettert, Catherine Woelfel, Thomas Engleitner, Isidro Cortes-Ciriano, Roland Rad, Wolfgang Herr, Bernd Giebel, Jurgen Ruland, Florian Bassermann, Christoph Coch, Gunther Hartmann, Hendrik Poeck
Summary: Tumor-derived extracellular vesicles (EVs) play a role in immune evasion and tumor progression through the RNA-sensing receptor RIG-I. Activation of RIG-I releases EVs that promote dendritic cell maturation and T cell antitumor immunity, synergizing with immune checkpoint blockade. Intact RIG-I, autocrine interferon signaling, and the GTPase Rab27a are necessary for the generation of immunostimulatory EVs. The composition of the EV RNA cargo, including small non-coding stimulatory RNAs, is regulated by active intrinsic RIG-I signaling. Increased transcriptional activity of EV pathway genes and RIG-I in melanoma samples is associated with prolonged patient survival and positive response to immunotherapy. EVs generated from human melanoma after RIG-I stimulation induce potent antigen-specific T cell responses.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Julian Kolorz, Salih Demir, Adrian Gottschlich, Iris Beirith, Matthias Ilmer, Daniel Luethy, Christoph Walz, Mario M. Dorostkar, Thomas Magg, Fabian Hauck, Dietrich von Schweinitz, Sebastian Kobold, Roland Kappler, Michael Berger
Summary: This study found that neurokinin-1 receptor is highly expressed in Rhabdoid tumors and demonstrated that the neurokinin-1 receptor antagonist aprepitant can serve as a novel therapeutic approach in treating Rhabdoid tumors.
Review
Oncology
Dania Briukhovetska, Janina Dorr, Stefan Endres, Peter Libby, Charles A. Dinarello, Sebastian Kobold
Summary: This article provides an update on the role of interleukins in tumor biology, highlighting their significance in cancer development, progression, and immunotherapy. Interleukins can both promote cancer growth and enhance tumor-directed immune responses, making them a valuable target for improving treatment effectiveness and reducing side effects.
NATURE REVIEWS CANCER
(2021)
