Review
Biochemistry & Molecular Biology
Alberto Servetto, Luigi Formisano, Carlos L. Arteaga
Summary: FGFR signaling abnormalities play a role in breast cancer development and drug resistance. Clinical trials with FGFR inhibitors have faced challenges, with lack of established patient selection criteria identified as a potential reason for failure.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Cell Biology
Laura Pacini, Andrew D. Jenks, Nadia Carvalho Lima, Paul H. Huang
Summary: Lung cancer is the most common cause of cancer-related deaths globally, and genetic alterations in the FGFR family in non-small cell lung cancer play a role in cancer initiation and progression. Therapies targeting FGFR have been developed, but clinical trials have shown low efficacy in lung cancer patients with FGFR aberrations.
Article
Biochemistry & Molecular Biology
Giulia Romano, Patricia Le, Giovanni Nigita, Michela Saviana, Lavender Micalo, Francesca Lovat, Daniel del Valle Morales, Howard Li, Patrick Nana-Sinkam, Mario Acunzo
Summary: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation show a positive initial response to tyrosine kinase inhibitors (TKIs), but rapid resistance is often developed due to genetic alterations, including amplification of hepatocyte growth factor receptor (MET) and its abnormal activity. The role of RNA post-transcriptional modifications, specifically adenosine-to-inosine (A-to-I) RNA editing, in the aberrant expression of MET in cancer, particularly NSCLC, is not well-studied. In this study, the researchers investigated the effect of edited miR-411-5p on NSCLC cell lines and found that it directly targets MET and negatively affects the mitogen-activated protein kinases (MAPKs) pathway. By overexpressing edited miR-411-5p, the researchers observed reduced proliferation and increased apoptosis in TKI-resistant NSCLC cells, indicating a potential improvement in EGFR TKI response.
Article
Chemistry, Multidisciplinary
Meng-di Dai, Yue-liang Wang, Jun Fan, Yang Dai, Yin-chun Ji, Yi-ming Sun, Xia Peng, Lan-lan Li, Yu-ming Wang, Wen-hu Duan, Jian Ding, Jing Ai
Summary: DW14383 is a promising selective irreversible pan-FGFR inhibitor with pan-tumor spectrum potential in FGFR1-4 aberrant cancers, which has the potential to overcome compensatory activation among FGFR1-4.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Physiology
Zhuojun Guo, Xin Liao, J. -Y. Chen, Chunpeng He, Zuhong Lu
Summary: This study sequenced the full-length transcriptomes of four common reef-building corals and identified the budding-related FGF and FGFR genes. The 3D models and binding models of FGF and FGFR proteins were reconstructed, revealing similarities between some corals and hydra in terms of the FGF8-FGFR3 binding model. This research provides background information for the potential budding propagation signaling pathway and aids in the future restoration of coral reefs.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Oncology
Sitong Yue, Yukun Li, Xiaojuan Chen, Juan Wang, Meixiang Li, Yongheng Chen, Daichao Wu
Summary: This review discusses the mechanisms of resistance to FGFR-TKI in cancer and strategies to overcome resistance, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. Potential strategies to overcome resistance include developing covalent inhibitors, dual-target inhibitors, combination therapy, and targeting lysosomes to transition to precision medicine and individualized treatment.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Jia Zheng, Wei Zhang, Linfeng Li, Yi He, Yue Wei, Yongjun Dang, Shenyou Nie, Zufeng Guo
Summary: Targeted therapy is a groundbreaking innovation in cancer treatment, with FGFRs being recognized as promising therapeutic targets. Several generations of FGFR kinase inhibitors have been developed over the past two decades.
FRONTIERS IN CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Qian Jin, Feihua Huang, Xianrong Xu, Haidong He, Yingqing Zhang
Summary: The study found that the expression of HIF-1 alpha in EGFR-TKIs sensitive NSCLC tissue was significantly higher, and the level of HIF-1 alpha increased further after acquiring resistance. There was a negative correlation between HIF-1 alpha level and the occurrence time of acquired resistance as well as the acquired EGFR T790M mutation.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Manali Tilak, Jennifer Holborn, Laura A. New, Jasmin Lalonde, Nina Jones
Summary: Glioblastoma multiforme (GBM) is a deadly cancer with limited response to existing therapies. Subtypes of GBM with distinct genetic signatures show aberrant activation of signal transduction pathways. Current research focuses on understanding these molecular alterations to develop more efficient targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Amanpreet Kaur, Debasish Mandal
Summary: This study focuses on computational investigations for the discovery of novel FGFR inhibitors. Through pharmacophore modeling, virtual screening, docking, ADMET analysis, molecular dynamics, and knowledge-based structure-activity relationship, four potential compounds were identified and analyzed for drug-likeness and stability.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Cell Biology
Andrea Napolitano, Alexandra E. Ostler, Robin L. Jones, Paul H. Huang
Summary: FGFR pathway alterations have been identified in various sarcoma subtypes, suggesting potential therapeutic targets. However, clinical trials have shown low efficacy of selective FGFR inhibitors, highlighting the need for further research to identify patients who will benefit most from this targeted therapy.
Article
Biochemistry & Molecular Biology
Neil Bate, James Lodge, Nicholas P. J. Brindle
Summary: This study enhanced the binding affinity of Tie2 Ectodomain trap for Ang2 using directed protein evolution and revealed different contributions of Tie2 residues to binding of Ang1 and Ang2. It also identified selectivity-determining residues that could be targeted for the design of inhibitors of Ang2 in the treatment of vascular dysfunction.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Oncology
Paula Aldaz, Imanol Arozarena
Summary: Glioblastoma (GBM) is the most common and lethal form of malignant brain tumor, and patients typically undergo surgery followed by radiotherapy and chemotherapy. Despite promising preclinical evidence, clinical trials testing the therapeutic potential of tyrosine kinase inhibitors (TKIs) targeting EGFR, PDGF receptors, and other tyrosine kinases have not led to significant breakthroughs in treating GBM over the past two decades. This article critically analyzes the reasons for the failure of TKIs in GBM treatment and proposes alternative approaches for the evaluation of TKIs in GBM patients.
Article
Multidisciplinary Sciences
Hoai-Nghia Nguyen, Ngoc-Phuong Thi Cao, Thien-Chi Van Nguyen, Khang Nguyen Duy Le, Dat Thanh Nguyen, Quynh-Tho Thi Nguyen, Thai-Hoa Thi Nguyen, Chu Van Nguyen, Ha Thu Le, Mai-Lan Thi Nguyen, Trieu Vu Nguyen, Vu Uyen Tran, Bac An Luong, Linh Gia Hoang Le, Quoc Chuong Ho, Hong-Anh Thi Pham, Binh Thanh Vo, Luan Thanh Nguyen, A. nh-Thu Huynh Dang, Sinh Duy Nguyen, Duc Minh Do, Thanh-Thuy Thi Do, Anh Vu Hoang, Kiet Truong Dinh, Minh-Duy Phan, Hoa Giang, Le Son Tran
Summary: The use of liquid biopsy in NSCLC patients undergoing TKI therapy revealed diverse profiles of resistance mutations, with EGFR amplification possibly linked to genome instability and hypomethylation, and hypermethylation observed in regulatory regions of Homeobox genes. Amplification of MET and HER2 did not show similar changes in methylation. Liquid biopsy provides important insights into TKI resistance mechanisms for prediction and selection of subsequent treatment.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Jing Zhu, Qian Yang, Weiguo Xu
Summary: Molecular targeted therapy offers a more precise approach to treating NSCLC patients with EGFR mutations. Various therapeutic agents targeting EGFR mutations have been approved or are in clinical trials worldwide, showing promise for a more personalized and effective treatment strategy.