Review
Chemistry, Medicinal
Adileh Ayati, Setareh Moghimi, Mahsa Toolabi, Alireza Foroumadi
Summary: Despite advancements in cancer treatment, EGFR inhibitors have shown significant improvement in targeted therapy. However, the emergence of epigenetic mutation and resistance issues have limited their effectiveness, leading to the need for further research in this field. Recent studies have focused on genetic alterations in the EGFR tyrosine kinase domain, resulting in the development of more selective and effective inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
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
Cardiac & Cardiovascular Systems
Ryo Miyata, Masatsugu Hamaji, Atsushi Kawaguchi, Yumeta Shimazu, Masaki Ikeda, Masashi Ishikawa, Hidenao Kayawake, Toshi Menju, Masashi Kobayashi, Norihito Okumura, Yasuto Sakaguchi, Makoto Sonobe, Akira Matsumoto, Tsuyoshi Shoji, Hiromichi Katakura, Ryota Sumitomo, Cheng-Long Huang, Mamoru Takahashi, Akihiro Aoyama, Yusuke Muranishi, Tomoya Kono, Ryo Miyahara, Naoki Date, Takuji Fujinaga, Ei Miyamoto, Tatsuo Nakagawa, Takahisa Fukada, Hiroaki Sakai, Hiroshi Date
Summary: This study analyzed the long-term survival outcomes and prognostic factors of patients with postoperative recurrent EGFR-mutated lung adenocarcinoma who received EGFR-TKIs as first-line treatment. The study found that first-line EGFR-TKI treatment was generally associated with favorable survival outcomes. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter progression-free survival (PFS).
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Review
Pharmacology & Pharmacy
Jazlyn P. Borges, Katrina Mekhail, Gregory D. Fairn, Costin N. Antonescu, Benjamin E. Steinberg
Summary: Chronic pain is a major public health issue that is often resistant to conventional analgesics. Recent studies have implicated the epidermal growth factor receptor (EGFR) signaling pathway in chronic pain, suggesting potential therapeutic targets for this devastating condition.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Nicolas Joly-Tonetti, Thomas Ondet, Mario Monshouwer, Georgios N. Stamatas
Summary: Cutaneous adverse drug reactions (CADR) associated with oncology therapy are common in patients receiving kinase inhibitors, particularly Epidermal Growth Factor Receptor inhibitors (EGFRi). EGFRi directly affect basal keratinocyte growth and differentiation, leading to skin barrier impairment. Conversely, pan-kinase inhibitors targeting VEGFR mainly promote keratinocyte proliferation without affecting differentiation. Overall, this study contributes to the understanding of EGFRi's specific mode of action in causing CADR.
Review
Oncology
Melissa Johnson, Marina Chiara Garassino, Tony Mok, Tetsuya Mitsudomi
Summary: Tyrosine kinase inhibitors (TKIs) are the standard treatment for patients with EGFR-mutant non-small cell lung cancer (NSCLC). Despite the initial effectiveness of TKIs, almost all patients eventually develop resistance. Current research focuses on developing novel therapies to overcome resistance mechanisms.
Article
Multidisciplinary Sciences
Hyoung-oh Jeong, Hayoon Lee, Hyemin Kim, Jinho Jang, Seunghoon Kim, Taejoo Hwang, David Whee-Young Choi, Hong Sook Kim, Naeun Lee, Yoo Mi Lee, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Semin Lee, Se-Hoon Lee
Summary: The study found that specific cell types such as lung epithelial precursor cells and transitional effector T cells, as well as an immunosuppressive microenvironment, were enriched in the MPE of EGFR TKI-resistant patients, potentially associated with their response to TKI therapy.
Article
Chemistry, Medicinal
Meredith S. Eno, Jason D. Brubaker, John E. Campbell, Chris De Savi, Timothy J. Guzi, Brett D. Williams, Douglas Wilson, Kevin Wilson, Natasja Brooijmans, Joseph Kim, Aysegul Ozen, Emanuele Perola, John Hsieh, Victoria Brown, Kristina Fetalvero, Andrew Garner, Zhuo Zhang, Faith Stevison, Rich Woessner, Jatinder Singh, Yoav Timsit, Caitlin Kinkema, Clare Medendorp, Christopher Lee, Faris Albayya, Alena Zalutskaya, Stefanie Schalm, Thomas A. Dineen
Summary: While EGFR tyrosine kinase inhibitors have revolutionized the treatment of NSCLC, the development of resistance mutations remains a challenge. This study introduces a novel reversible inhibitor, BLU-945, that shows promising activity against different resistance mutations. Clinical trials are currently underway to evaluate its efficacy and safety.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Karam Khaddour, Sushma Jonna, Alexander Deneka, Jyoti D. Patel, Mohamed E. Abazeed, Erica Golemis, Hossein Borghaei, Yanis Boumber
Summary: EGFR mutations are common in lung cancer patients, and EGFR TKIs have become the standard of care with high response rates initially, but resistance remains a major challenge. Ongoing research aims to understand resistance mechanisms and evaluate novel agents and combination therapies to overcome this resistance. Recent breakthroughs highlight the use of EGFR TKIs in non-metastatic EGFR-mutated lung cancer.
Article
Chemistry, Medicinal
Jing Zhu, Yalun Li, Xiaoai Wu, Yunchun Li, Li Wang, Hong Fan
Summary: This article reviews the progress and applications of small molecular tyrosine kinase-targeted PET tracers, as well as their importance in personalized non-small-cell lung cancer treatment and prediction of clinical response.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
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.
Review
Oncology
Yuzhong Chen, Shaodi Wen, Yuan Wu, Lin Shi, Xiaoyue Xu, Bo Shen
Summary: The meta-analysis of randomized controlled trials showed that first-generation EGFR-TKIs combined with chemotherapy or antiangiogenic therapy led to significant improvements in objective response rate, disease control rate, progression-free survival, and overall survival compared to monotherapy in patients with EGFR-mutated advanced non-small cell lung cancer.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paola Ulivi, Elisabetta Petracci, Matteo Canale, Ilaria Priano, Laura Capelli, Daniele Calistri, Elisa Chiadini, Paola Cravero, Alice Rossi, Angelo Delmonte, Lucio Crino, Giuseppe Bronte
Summary: The study found that liquid biopsy can be used as an alternative for EGFR detection in treatment-naive patients and those who have already undergone tumor biopsy. Most liquid biopsy analyses were done in NSCLC patients progressing during TKI therapy. The presence of EGFR mutation in cfDNA was associated with a worse prognosis, while in two patients, VAF of EGFR mutations in cfDNA correlated with tumor volume changes.
Review
Oncology
Daisy Wai-Ka Chan, Horace Cheuk-Wai Choi, Victor Ho-Fun Lee
Summary: This study conducted a systematic review and meta-analysis to investigate the treatment-related adverse events (trAEs) of combined epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) in advanced non-small cell lung cancer (NSCLC). The results demonstrated a higher incidence of grade >= 3 trAEs in combination TKI and ICI, particularly in skin, gastrointestinal tract, and interstitial lung diseases. However, the interpretation of these results should be cautious due to the limited number of studies included in this meta-analysis.
Article
Oncology
Marianna Carrabotta, Maria Antonella Laginestra, Giorgio Durante, Caterina Mancarella, Lorena Landuzzi, Alessandro Parra, Francesca Ruzzi, Lisa Toracchio, Alessandra De Feo, Veronica Giusti, Michela Pasello, Alberto Righi, Pier-Luigi Lollini, Emanuela Palmerini, Davide Maria Donati, Maria Cristina Manara, Katia Scotlandi
Summary: CIC-DUX4-rearranged sarcomas, specifically Capicua-double homeobox 4 (CIC-DUX4)-rearranged sarcomas (CDS), are rare and aggressive tumors that require specific therapeutic approaches. This study identified a unique HMGA2/IGF2BP/IGF2/IGF1R/AKT/mTOR axis in CDS, indicating sensitivity to combined treatments with trabectedin and PI3K/mTOR inhibitors. The development of representative experimental models (PDXs and PDX-derived cell lines) has highlighted the potential of AKT/mTOR inhibitors and trabectedin in combating this lethal cancer.
Article
Oncology
Tommaso Balestra, Maria Cristina Manara, Maria Antonella Laginestra, Michela Pasello, Alessandra De Feo, Cristian Bassi, Clara Guerzoni, Lorena Landuzzi, Pier-Luigi Lollini, Davide Maria Donati, Massimo Negrini, Mauro Magnani, Katia Scotlandi
Summary: The modulation of CD99 in Ewing sarcoma may alter transcriptional dysregulation and affect the development of the tumor by controlling the zyxin-GLI1 axis.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Katsuhiro Togami, Sun Sook Chung, Vikas Madan, Christopher A. G. Booth, Christopher M. Kenyon, Lucia Cabal-Hierro, Justin Taylor, Sunhee S. Kim, Gabriel K. Griffin, Mahmoud Ghandi, Jia Li, Yvonne Y. Li, Fanny Angelot-Delettre, Sabeha Biichle, Michael Seiler, Silvia Buonamici, Scott B. Lovitch, Abner Louissaint, Elizabeth A. Morgan, Fabrice Jardin, Pier Paolo Piccaluga, David M. Weinstock, Peter S. Hammerman, Henry Yang, Marina Konopleva, Naveen Pemmaraju, Francine Garnache-Ottou, Omar Abdel-Wahab, H. Phillip Koeffler, Andrew A. Lane
Summary: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia primarily occurring in males, and the mutations in X chromosome gene ZRSR2 are associated with impaired dendritic cell function and predisposition to leukemic transformation.
Article
Cell Biology
Francesca Chiarini, Francesca Paganelli, Tommaso Balestra, Cristina Capanni, Antonietta Fazio, Maria Cristina Manara, Lorena Landuzzi, Stefania Petrini, Camilla Evangelisti, Pier-Luigi Lollini, Alberto M. Martelli, Giovanna Lattanzi, Katia Scotlandi
Summary: Lamin A plays a significant role in Ewing Sarcoma by affecting cell migration and invasiveness. Low expression of Lamin A is associated with increased aggressiveness and metastatic load in patients. This effect is linked to altered nuclear envelope proteins and increased nuclear retention of YAP/TAZ. Overexpression of Lamin A or pharmacological modulation of its maturation can prevent cell invasiveness and improve therapeutic strategies for Ewing Sarcoma.
CELL DEATH & DISEASE
(2022)
Article
Genetics & Heredity
Line J. Manceau, Julien E. Richard Albert, Pier-Luigi J. Lollini, Maxim V. C. E. Greenberg, Pascale J. Gilardi-Hebenstreit, Vanessa E. Ribes
Summary: The chimeric proteins PAX3-FOXO1 and PAX7-FOXO1, derived from chromosomal translocations, exhibit distinct genomic occupancy and transcriptional activity, leading to different pathological manifestations in alveolar rhabdomyosarcoma.
Article
Oncology
Carlo Sorrentino, Luigi D'Antonio, Stefania Livia Ciummo, Cristiano Fieni, Lorena Landuzzi, Francesca Ruzzi, Simone Vespa, Paola Lanuti, Lavinia Vittoria Lotti, Pier Luigi Lollini, Emma Di Carlo
Summary: IL30 plays a crucial role in the development and progression of prostate cancer by regulating tumor driver genes and immunity-related genes. Targeting IL30 using CRISPR/Cas9-mediated therapy shows promise for clinical application.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Michela Pasello, Anna Maria Giudice, Camilla Cristalli, Maria Cristina Manara, Caterina Mancarella, Alessandro Parra, Massimo Serra, Giovanna Magagnoli, Florencia Cidre-Aranaz, Thomas G. P. Grunewald, Carla Bini, Pier-Luigi Lollini, Alessandra Longhi, Davide Maria Donati, Katia Scotlandi
Summary: The study reveals that high expression of ABCA6 in Ewing sarcoma (EWS) is associated with a favorable outcome in patients. It functions as a tumor suppressor by regulating cholesterol levels and inhibiting IGF1R/AKT/MDM2 signaling, leading to reduced cell migration and increased sensitivity to chemotherapy. These findings support the use of ABCA6 as a biomarker for EWS progression and the consideration of statins as adjuvant drugs.
Article
Biochemistry & Molecular Biology
Francesca Ruzzi, Arianna Palladini, Stine Clemmensen, Anette Strobaek, Nicolaas Buijs, Tanja Domeyer, Jerzy Dorosz, Vladislav Soroka, Dagmara Grzadziela, Christina Jo Rasmussen, Ida Busch Nielsen, Max Soegaard, Maria Sofia Semprini, Laura Scalambra, Stefania Angelicola, Lorena Landuzzi, Pier-Luigi Lollini, Mette Thorn
Summary: The ES2B-C001 vaccine shows promising preclinical activity in the treatment of HER-2(+) breast cancer, effectively inhibiting tumor growth and metastasis. Vaccination induces strong antibody responses and does not cause cytokine storms. These results provide a basis for further human clinical studies.
Correction
Oncology
Michela Pasello, Anna Maria Giudice, Camilla Cristalli, Maria Cristina Manara, Caterina Mancarella, Alessandro Parra, Massimo Serra, Giovanna Magagnoli, Florencia Cidre-Aranaz, Thomas G. P. Grunewald, Carla Bini, Pier-Luigi Lollini, Alessandra Longhi, Davide Maria Donati, Katia Scotlandi
Review
Oncology
Lorena Landuzzi, Francesca Ruzzi, Pier-Luigi Lollini, Katia Scotlandi
Summary: Synovial sarcoma is a rare malignant tumor characterized by t(X;18) translocation encoding the SS18-SSX fusion gene, which interacts with BAF enhancer and polycomb repressor complexes to regulate gene transcription. Different experimental in vivo models for synovial sarcoma research include transgenic mouse models, patient-derived xenografts, and cell lines. These models have contributed to identifying vulnerabilities and developing new therapies for synovial sarcoma.
Article
Oncology
Giuseppe Visani, Maryam Etebari, Fabio Fuligni, Antonio Di Guardo, Alessandro Isidori, Federica Loscocco, Stefania Paolini, Mohsen Navari, Pier Paolo Piccaluga
Summary: Using next generation sequencing, this study found that genetic lesions characteristic of primary myelofibrosis occur at an early stage of hematopoietic stem cell differentiation. This sheds light on the complex transformation of pluripotent precursors in the development of the disease.
Article
Oncology
Elisabetta Setola, S. Benini, A. Righi, G. Gamberi, E. Carretta, C. Ferrari, S. Avnet, E. Palmerini, G. Magagnoli, M. Gambarotti, P. L. Lollini, M. Cesari, S. Cocchi, A. Paioli, A. Longhi, K. Scotlandi, M. A. Laginestra, D. M. Donati, N. Baldini, T. Ibrahim
Summary: This study found a higher frequency of IDH mutations in G3 CCBC compared to G2. No significant differences in overall survival, relapse-free survival, and progression-free survival were observed based on the mutational status. After relapse, a higher rate of G3 was observed in IDH mutated CCBC.
Review
Oncology
Lorena Landuzzi, Maria Cristina Manara, Laura Pazzaglia, Pier-Luigi Lollini, Katia Scotlandi
Summary: Synovial sarcoma (SyS) is a rare aggressive soft tissue sarcoma with a unique genetic signature. The majority of patients are initially diagnosed with localized disease, but metastatic relapse is common and advanced stages have a poor prognosis. This review summarizes current treatments and highlights the potential of new epigenetic and immunological strategies. Accurate patient selection based on genetic and tumor immune microenvironment signatures is crucial.
Article
Oncology
Anna Gazzola, Mohsen Navari, Claudia Mannu, Riccardo Donelli, Maryam Etebari, Pier Paolo Piccaluga
Summary: This study compared the diagnostic accuracy of the first commercially available next-generation sequencing (NGS) approaches with the current gold standard methods for evaluating immunoglobulin heavy chain gene rearrangements. The results showed that NGS-based clonality and somatic hypermutation analyses gave comparable results to conventional Sanger sequencing.
Review
Biochemistry & Molecular Biology
Francesca Ruzzi, Maria Sofia Semprini, Laura Scalambra, Arianna Palladini, Stefania Angelicola, Chiara Cappello, Olga Maria Pittino, Patrizia Nanni, Pier-Luigi Lollini
Summary: Cancer vaccines are being studied to prevent and treat cancers. Prophylactic vaccines for virus-caused cancers are already approved and used globally, while therapeutic cancer vaccines still need further development. Virus-like particles (VLPs) are protein structures designed to mimic viruses and can trigger immune responses. This review provides an overview of preventive VLP-based vaccines approved worldwide for HBV and HPV infections, and evaluates their effectiveness in preventing virus-caused cancers. It also summarizes preclinical and early clinical data on VLP-based cancer vaccines, focusing on HER-2-positive breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)