Review
Immunology
Ding-Yu Rao, De-Fa Huang, Mao-Yan Si, Hua Lu, Zhi-Xian Tang, Zu-Xiong Zhang
Summary: As an important mediator of information transfer between cells, exosomes play a unique role in regulating tumor growth, supporting vascular proliferation, tumor invasion, and metastasis. Exosomes can be used as a potential tool for non-invasive liquid biopsy due to their presence in various body fluids. This study reviews the role of exosomes in liquid biopsy, tumor microenvironment formation, and epithelial-mesenchymal transition in non-small cell lung cancer (NSCLC). It also discusses the occurrence of EGFR+ exosomes and the role of exosomes and their contents in non-invasive detection and potential therapeutic targets in EGFR-mutated lung cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Sangah Lee, Jiyae Jung, Yu-Jin Lee, Seon-Kyu Kim, Jung-Ae Kim, Bo-Kyung Kim, Kyung Chan Park, Byoung-Mog Kwon, Dong Cho Han
Summary: The study identified HSF1 as a potential target protein to overcome EGFR-TKI resistance in NSCLC, demonstrating the efficacy of HSF1 inhibition in vitro and in vivo. This suggests a targetable HSF1 pathway to overcome multiple mechanisms of EGFR-TKI resistance.
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
Multidisciplinary Sciences
Juliann Chmielecki, Jhanelle E. Gray, Ying Cheng, Yuichiro Ohe, Fumio Imamura, Byoung Chul Cho, Meng-Chih Lin, Margarita Majem, Riyaz Shah, Yuri Rukazenkov, Alexander Todd, Aleksandra Markovets, J. Carl Barrett, Ryan J. Hartmaier, Suresh S. Ramalingam
Summary: By sequencing circulating tumor DNA in patients from the FLAURA trial, this study identifies MET amplification and EGFR C797S mutation as the most frequent acquired resistance mechanisms to first-line osimertinib.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Baijiao An, Jian Liu, Yangyang Fan, Wenyan Nie, Chunhua Yang, Han Yao, Wei Li, Yin Zhang, Xingshu Li, Geng Tian
Summary: In this study, a new selective third-generation EGFR inhibitor, compound 6a, was identified with good inhibitory activity against EGFR mutant cells. Compound 6a also strongly affected EGFR-mediated signaling pathways, inhibited tumor proliferation, induced apoptosis, and showed efficacy in suppressing tumor growth in vivo. Therefore, compound 6a could be a promising lead compound for overcoming clinical EGFR T790M resistance in NSCLC patients.
BIOORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yun-Chieh Tu, Wei-Chen Yeh, Hsin-Hsien Yu, Yu-Cheng Lee, Bor-Chyuan Su
Summary: Non-small cell lung cancer (NSCLC) is a common and deadly cancer. Chemotherapy is the main treatment option for NSCLC patients with wild-type epidermal growth factor receptor (EGFR WT), but they have poor response to chemotherapy. This study found that hedgehog signaling is highly active in EGFR WT NSCLC cells and inhibiting this signaling can increase sensitivity to chemotherapy drug PTX.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Carolin Selenz, Anik Compes, Marieke Nill, Sven Borchmann, Margarete Odenthal, Alexandra Florin, Johannes Braegelmann, Reinhard Buettner, Lydia Meder, Roland T. Ullrich
Summary: EGFR inhibition promotes immune cell infiltration in the tumour microenvironment and enhances response to immune checkpoint inhibitors in EGFR-driven lung cancer.
Review
Biochemistry & Molecular Biology
Sarah Sayed Hassanein, Sherif Abdelaziz Ibrahim, Ahmed Lotfy Abdel-Mawgood
Summary: Lung cancer is a complex disease associated with gene mutations, particularly KRAS and EGFR. miRNAs play a key role in regulating EGFR crosstalk, affecting sensitivity to EGFR-TKI treatment, and can be used as diagnostic, prognostic, and therapeutic targets in NSCLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Mari Tone, Kota Iwahori, Takayuki Shiroyama, Shinji Futami, Yujiro Naito, Kiyoharu Fukushima, Kotaro Miyake, Shohei Koyama, Haruhiko Hirata, Izumi Nagatomo, Hisashi Wada, Yoshito Takeda, Atsushi Kumanogoh
Summary: Minocycline administration in NSCLC patients treated with first-line EGFR-TKIs was found to correlate with longer PFS and OS, independent of skin rash. This retrospective analysis suggests that minocycline may have a positive impact on the treatment outcomes of EGFR-mutant NSCLC patients.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Kazuya Nishii, Kadoaki Ohashi, Shuta Tomida, Takamasa Nakasuka, Atsuko Hirabae, Sachi Okawa, Jun Nishimura, Hisao Higo, Hiromi Watanabe, Hirohisa Kano, Chihiro Ando, Go Makimoto, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Heiichiro Udono, Yoshinobu Maeda, Katsuyuki Kiura
Summary: EGFR-mutant NSCLC has a noninflamed tumor microenvironment with weak response to immune-checkpoint inhibitors. EGFR-tyrosine kinase inhibitor can induce CD8+ T-cell responses, which are further enhanced by the dual blockade of PD-1 and VEGFR2. These findings could aid in developing alternative immunotherapy strategies for patients with driver mutations and a noninflamed tumor microenvironment.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Jung Hee Cho, Yeon-Mi You, Han Koo, Dong Chul Lee, Young Il Yeom, Kyung Chan Park
Summary: This study identified LPIN1 as a key factor in regulating gefitinib resistance in EGFR-mutant NSCLC cells, and found that LPIN1 expression was induced following gefitinib treatment, leading to increased lipid droplet formation and activation of protein kinase C delta and nuclear factor kappa B. Targeting LPIN1 was shown to synergistically inhibit tumor growth, suggesting a potential effective strategy for preventing TKI resistance in NSCLC patients.
Article
Oncology
Francesca Iommelli, Viviana De Rosa, Cristina Terlizzi, Rosa Fonti, Rosa Camerlingo, Maria Patrizia Stoppelli, C. Allison Stewart, Lauren Averett Byers, David Piwnica-Worms, Silvana Del Vecchio
Summary: Notch1 and EGFR are two different surface receptors in cancer cells, with high levels of active Notch1 leading to resistance to EGFR inhibitors by regulating the promoter activity of the EGFR gene and causing a reversible shift of driver dependence from EGFR to Notch1.
Article
Medicine, Research & Experimental
Xishan Chen, Renba Liang, Huan Lin, Kaihua Chen, Li Chen, Ge Tian, Xiaodong Zhu
Summary: Downregulation of CD166 inhibited CSC-related genes and decreased pEGFR and pERK expression in vitro and in vivo. The sphere formation and tumorigenesis ability of CD166-shRNA cells were significantly reduced. Additionally, EGF-stimulated CD166-shRNA cells showed an increase in CSC-like traits by activating the EGFR/ERK1/2 signaling pathway.
Article
Oncology
Hua Zhong, Xueyan Zhang, Panwen Tian, Tianqing Chu, Qisen Guo, Xinmin Yu, Zhuang Yu, Yalun Li, Lijuan Chen, Jie Liu, Yan Zhang, Yan Guan, Xun Shi, Jing Wang, Yanqiu Zhao, Baohui Han
Summary: This study evaluated the efficacy and safety of tislelizumab plus chemotherapy in EGFR-mutated non-squamous NSCLC patients after EGFR TKI failure. The results showed that tislelizumab plus chemotherapy is effective with an acceptable safety profile.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Pathology
Roberta Sgariglia, Mariantonia Nacchio, Ilaria Migliatico, Elena Vigliar, Umberto Malapelle, Pasquale Pisapia, Caterina De Luca, Antonino Iaccarino, Domenico Salvatore, Stefania Masone, Giancarlo Troncone, Claudio Bellevicine
Summary: The study developed and validated a novel custom NGS panel, Nexthyro, targeting 264 clinically relevant mutations in thyroid tumourigenesis. Nexthyro exhibited 100% specificity and detected more clinically relevant mutations compared with the 7-gene test in 5/72 FNAs. The results suggest that Nexthyro is a reliable NGS panel, providing affordable access to NGS for patients with undetermined thyroid nodules.
JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Pathology
Umberto Malapelle, Francesco Pepe, Pasquale Pisapia, Annalisa Altimari, Claudio Bellevicine, Hans Brunnstrom, Rossella Bruno, Reinhard Buttner, Luis Cirnes, Carlos E. De Andrea, Dario de Biase, Catherine Dumur, Kajsa Ericson Lindquist, Gabriella Fontanini, Eugenio Gautiero, David Gentien, Paul Hofman, Veronique Hofman, Antonino Iaccarino, Maria Dolores Lozano, Clara Mayo-de-Las-Casas, Sabine Merkelbach-Bruse, Fabio Pagni, Ruth Roman, Fernando C. Schmitt, Janna Siemanowski, Sinchita Roy-Chowdhuri, Giovanni Tallini, Francesc Tresserra, Sara Vander Borght, Philippe Vielh, Elena Vigliar, Giulia Anna Carmen Vita, Birgit Weynand, Rafael Rosell, Miguel Angel Molina Vila, Giancarlo Troncone
Summary: Gene fusion assays are crucial for personalized treatments of advanced human cancers. This study developed and validated gene fusion reference standards using cell line slides, finding that better results were obtained with Pap staining and amplicon-based assays. Further optimization is required for MGG stained cells and hybridisation-based approaches.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Pathology
Paola Parente, Umberto Malapelle, Valentina Angerilli, Mariangela Balistreri, Sara Lonardi, Salvatore Pucciarelli, Caterina De Luca, Francesco Pepe, Gianluca Russo, Elena Vigliar, Angela Danza, Fabio Scaramuzzi, Giancarlo Troncone, Paolo Graziano, Matteo Fassan
Summary: This study assessed the concordance rate of MMR/MSI status between primary mucinous adenocarcinoma (MA) and synchronous metastasis. The results showed high concordance rates using different evaluation methods. Therefore, integrating immunohistochemistry evaluation and molecular methods may be beneficial for molecular profiling of MA patients.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Pathology
Gianluca Russo, Francesco Pepe, Pasquale Pisapia, Lucia Palumbo, Mariantonia Nacchio, Elena Vigliar, Pierlorenzo Pallante, Paola Parente, Matteo Fassan, Paolo Graziano, Claudio Bellevicine, Giancarlo Troncone, Umberto Malapelle, Antonino Iaccarino
Summary: This article reviews the results of microsatellite instability (MSI) evaluation using a customized workflow and microfluidic system in a diagnostic routine practice over a period of 4 years. The results showed that the majority of patients with metastatic colorectal cancer (mCRC) had microsatellite stability (MSS) profile, while a minority had microsatellite high (MSI-H) profile. Similarly, in patients without colorectal cancer, both MSS and MSI-H profiles were observed.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Pathology
Silvia Bessi, Francesco Pepe, Gianluca Russo, Pasquale Pisapia, Marco Ottaviantonio, Francesca Biancalani, Antonino Iaccarino, Maria Russo, Mauro Biancalani, Giancarlo Troncone, Umberto Malapelle
Summary: In the era of personalised medicine, testing for predictive biomarkers has become increasingly important. Circulating tumour DNA (ctDNA) is being recognized as a valuable source for biomarker testing. This study evaluated the reproducibility of using Illumina MiSeq and Thermo Fisher Ion S5 Plus platforms to assess pathogenic alterations in non-small cell lung cancer (NSCLC) liquid biopsy specimens. The study found a high degree of concordance between the two methodologies.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Letter
Oncology
Maria Jose Serrano, Umberto Malapelle
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Health Care Sciences & Services
Alessandro Mangogna, Giada Munari, Francesco Pepe, Edoardo Maffii, Pierluigi Giampaolino, Giuseppe Ricci, Matteo Fassan, Umberto Malapelle, Stefania Biffi
Summary: Homologous recombination deficiency (HRD) refers to the inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway. It serves as a predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD is a complex genomic signature, and various methods of analysis have been developed for HRD testing in the clinical setting.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Oncology
Vassilios Gavriil, Angelo Ferraro, Alkiviadis-Constantinos Cefalas, Zoe Kollia, Francesco Pepe, Umberto Malapelle, Caterina De Luca, Giancarlo Troncone, Evangelia Sarantopoulou
Summary: This study advances the prognosis of metastatic colorectal cancer by identifying morphological markers from atomic force microscopy (AFM) images. It achieves a spatial resolution of 97.7 nm by using variograms and Gaussian filtering. Early detection of metastatic tumor phases is crucial for improving cancer survival and accurately predicting disease advancement.
Article
Medicine, General & Internal
Paolo Bironzo, Francesco Pepe, Gianluca Russo, Pasquale Pisapia, Gianluca Gragnano, Gabriella Aquino, Silvia Bessi, Simonetta Buglioni, Federico Bartoccini, Giuseppina Ferrero, Michela Anna Bresciani, Paola Francia di Celle, Francesca Sibona, Andrea Giusti, Alessandra Movilia, Renata Mariella Farioli, Alessandra Santoro, Domenico Salemi, Stefania Scarpino, Dino Galafate, Stefania Tommasi, Rosanna Lacalamita, Davide Seminati, Elham Sajjadi, Silvia Novello, Fabio Pagni, Giancarlo Troncone, Umberto Malapelle
Summary: Lung cancer is the leading cause of cancer deaths worldwide. The molecular analysis of MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping has been promoted for the stratification of non-small cell lung cancer (NSCLC) patients. Different testing strategies for MET exon 14 skipping were evaluated for their technical performance and reproducibility in various centers. The use of artificial reference slides proved to be a valid tool for harmonizing technical workflows in the evaluation of MET exon 14 skipping molecular alterations in routine practice.
Article
Oncology
Diego de Miguel-Perez, Edward M. Pickering, Umberto Malapelle, William Grier, Francesco Pepe, Pasquale Pisapia, Gianluca Russo, Joseph A. Pinto, Alessandro Russo, Giancarlo Troncone, Melissa J. Culligan, Katherine A. Scilla, Ranee Mehra, Pranshu Mohindra, Oscar Arrieta, Andres F. Cardona, Marzia Del Re, Ashutosh Sachdeva, Fred R. Hirsch, Andrea Wolf, Joseph S. Friedberg, Christian Rolfo
Summary: In this study, genetic alterations in resectable pleural mesothelioma tissues and blood samples were analyzed, and it was found that high tissue tumor mutational burden, tissue median minor allele frequency, blood tumor mutational burden, and specific mutations were correlated with outcomes in patients with resected PM. These findings suggest that molecular profiling could help identify longer survivors in patients with resected PM.
EUROPEAN JOURNAL OF CANCER
(2024)
Review
Medicine, General & Internal
Martina Ferrara, Basilio Pecorino, Maria Gabriella D'Agate, Giuseppe Angelico, Ettore Domenico Capoluongo, Umberto Malapelle, Francesco Pepe, Paolo Scollo, Liliana Mereu
Summary: UTROSCT is a rare uterine tumor with a generally favorable prognosis, but it can also present as advanced and distant recurrences. Molecular studies and sequencing can help identify high-risk patients.
JOURNAL OF CLINICAL MEDICINE
(2023)