Article
Medicine, Research & Experimental
Ji-Yon Shin, Sung-Min Ahn
Summary: The study found that Src plays a crucial role in the endosomal delivery of the FGFR4 signaling complex in HCC. This provides a scientific rationale for repurposing Src inhibitors for the treatment of HCCs with activated FGFR4 pathway.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Xuesong Zhao, Jaya Julie Joshi, Daniel Aird, Craig Karr, Kun Yu, Chialing Huang, Federico Colombo, Milena Virrankoski, Sudeep Prajapati, Anand Selvaraj
Summary: The combination therapy of Lenvarinib and FGFR4 inhibitor shows enhanced efficacy for the treatment of FGF19-driven hepatocellular carcinoma by increasing anti-angiogenic and anti-tumorigenic activities.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Chemistry, Medicinal
Chenghao Pan, Wenwen Nie, Jiao Wang, Jiamin Du, Zhichao Pan, Jian Gao, Yang Lu, Jinxin Che, Hong Zhu, Haibin Dai, Binhui Chen, Qiaojun He, Xiaowu Dong
Summary: This study developed a series of quinazoline derivatives based on the FGFR4 inhibitor BLU9931, with compound 35a showing improved stability in liver microsomes and induced apoptosis via FGFR4 signaling pathway blockage. Computational simulation provided insights into the binding mode of compound 35a to FGFR4 protein, explaining its high potency and metabolic stability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tianli Chen, Hongda Liu, Zengli Liu, Kangshuai Li, Ruixi Qin, Yue Wang, Jialiang Liu, Zhipeng Li, Qinglun Gao, Chang Pan, Fan Yang, Wei Zhao, Zongli Zhang, Yunfei Xu
Summary: The study revealed that FGF19 and FGFR4 are adverse prognostic biomarkers for gallbladder carcinoma, with their co-expression being a more sensitive predictor. FGF19 can promote GBC progression by stimulating FGFR4 activation via an autocrine pathway with bile as a potential carrier.
Article
Chemistry, Medicinal
Yingyue Yang, Xiaojie He, Zulong Li, Kai Ran, Ningyu Wang, Lifeng Zhao, Zhihao Liu, Jun Zeng, Bo Chang, Qiang Feng, Qiangsheng Zhang, Luoting Yu
Summary: A series of 1H-indazole derivatives were designed and synthesized as new irreversible inhibitors of wildtype and gatekeeper mutant FGFR4. Compound 27i showed the most potent FGFR4 inhibitory activity (FGFR4 IC50 = 2.4 nM) and exhibited no activity against a panel of 381 kinases at 1 μM. It also demonstrated nanomolar IC50s against huh7 and two mutant cell lines, and potent antitumor potency in Huh7 xenograft mouse models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Xilang Chen, Jie Chen, Weibo Feng, Wenjie Huang, Guodong Wang, Mengyu Sun, Xiangyuan Luo, Yijun Wang, Yongzhan Nie, Daiming Fan, Kaichun Wu, Limin Xia
Summary: Elevated ELF4 expression is positively correlated with distant metastasis, advanced AJCC stages, and poor prognosis in colorectal cancer patients. ELF4 promotes CRC metastasis by transactivating its downstream target genes FGFR4 and SRC. FGF19 upregulates ELF4 expression through the ERK1/2/SP1 axis. Combination therapy with the FGFR4 inhibitor BLU-554 and the SRC inhibitor KX2-391 effectively suppresses ELF4-mediated CRC metastasis.
Article
Multidisciplinary Sciences
Zhanchao Tao, Yue Cui, Xilong Xu, Ting Han
Summary: Aberrant FGF19 signaling through FGFR4 and KLB plays a driving role in hepatocellular carcinoma. Selective inhibition of FGFR4 alone is not sufficient to inhibit cell proliferation and tumor growth in FGF19-positive HCC, while genetic inactivation of KLB results in a more severe fitness defect. KLB associates with FGFR3 and FGFR4 to mediate the prosurvival functions of FGF19. FGFR3 restricts the activity of FGFR4-selective inhibitors, and pan-FGFR inhibitor erdafitinib is more potent in suppressing the growth and survival of FGF19-positive HCC cells. FGFR3 is prevalently coexpressed with FGFR4 and KLB in FGF19-positive HCC cases, suggesting FGFR redundancy as a common mechanism underlying resistance to FGFR4 inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Pharmacology & Pharmacy
Hao Xie, Diego M. Alem Glison, Richard D. Kim
Summary: Aberrant FGF19/FGFR4 signaling is a driver of HCC cell growth and survival. Selective FGFR4 inhibitors show promise in clinical trials and demonstrate manageable on-target side effects. Emphasis should be placed on the development of predictive biomarkers and understanding of resistance mechanisms.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Oncology
Jianming Xu, Jiuwei Cui, Haiping Jiang, Yan Zeng, Xiuyu Cong
Summary: This study determined the MTD, RP2D, pharmacokinetics, safety, and preliminary efficacy of EVER4010001 plus pembrolizumab in patients with advanced solid tumors. The results showed that 80 mg BID was the MTD and RP2D for EVER4010001 plus pembrolizumab.
Article
Oncology
Liwei Lang, Yuanping Xiong, Nestor Prieto-Dominguez, Reid Loveless, Caleb Jensen, Chloe Shay, Yong Teng
Summary: The study found that high-dose melatonin has dose-dependent effects on migration and invasion of head and neck squamous cell carcinoma cells. High-dose melatonin promotes cell metastasis through the FGF19/FGFR4 signaling pathway and reverses its anti-metastasis function. Blocking the FGF19/FGFR4 signaling pathway may enhance the efficacy of melatonin in cancer treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Genhao Zhang, Xianping Lv, Qiankun Yang, Hongchun Liu
Summary: This study found that upregulated HM13 in HCC is associated with poor prognosis, enhanced proliferation and migration potential of HCC cells. Additionally, patients with high HM13 expression might be more sensitive to immunotherapy.
Article
Gastroenterology & Hepatology
Shuxia Tian, Min Chen, Bing Wang, Yonglong Han, Haonan Shang, Junming Chen
Summary: This study identified that salvianolic acid B derived from Salvia miltiorrhiza can inhibit the proliferation and activation of hepatic stellate cells (HSCs) by regulating the FGF19/FGFR4 signaling pathway, demonstrating its anti-fibrotic effects in liver fibrosis.
ANNALS OF HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Hiroaki Kanzaki, Tetsuhiro Chiba, Junjie Ao, Keisuke Koroki, Kengo Kanayama, Susumu Maruta, Takahiro Maeda, Yuko Kusakabe, Kazufumi Kobayashi, Naoya Kanogawa, Soichiro Kiyono, Masato Nakamura, Takayuki Kondo, Tomoko Saito, Ryo Nakagawa, Sadahisa Ogasawara, Eiichiro Suzuki, Yoshihiko Ooka, Ryosuke Muroyama, Shingo Nakamoto, Shin Yasui, Akinobu Tawada, Makoto Arai, Tatsuo Kanda, Hitoshi Maruyama, Naoya Mimura, Jun Kato, Yoh Zen, Masayuki Ohtsuka, Atsushi Iwama, Naoya Kato
Summary: Inhibiting FGFR4/ERK signaling can enhance the efficacy of MKI treatment in HCC. Serum FGF19 levels may serve as a predictive marker for drug response and survival in HCC patients treated with sorafenib.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Baozhu Zhang, Qing Zhou, Qiankun Xie, Xiaohui Lin, Wenqiang Miao, Zhaoguang Wei, Tingting Zheng, Zuoliang Pang, Haosheng Liu, Xi Chen
Summary: This study characterized the differential expression of SPC25 in HCC patients of different races and HBV infection status. The findings suggest that increased expression of SPC25 is associated with poor prognosis of HCC and enhances the proliferative capacity of HCC cells. SPC25 could serve as a valuable prognostic marker and a novel treatment target for HCC.
Article
Chemistry, Medicinal
Xiaolu Chen, Yanan Liu, Liting Zhang, Daoxing Chen, Zhaojun Dong, Chengguang Zhao, Zhiguo Liu, Qinqin Xia, Jianzhang Wu, Yongheng Chen, Xiaohui Zheng, Yuepiao Cai
Summary: In this study, a series of indazole derivatives were designed and synthesized, with F-30 showing subtle selectivity for FGFR4 and affecting cell growth and migration in HCC cell lines by inhibiting FGFR4 pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Hyo Jeong Kang, Farhan Haq, Chang Ohk Sung, Jene Choi, Seung-Mo Hong, Soo-Heang Eo, Hui Jeong Jeong, Jinho Shin, Ju Hyun Shim, Han Chu Lee, Jihyun An, Mi-Ju Kim, Kyu-pyo Kim, Sung-Min Ahn, Eunsil Yu
Article
Biotechnology & Applied Microbiology
Su Young Kim, Eun Chan Mun, Jun-Won Chung, Minsu Ha, Sung-Min Ahn, Mun-Deok Han, Sang-Hun Han, Sung-Cheol Yun, Jung Ho Kim, Kyoung Oh Kim, Yoon Jae Kim, Kwang An Kwon, Dong Kyun Park
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
(2019)
Article
Genetics & Heredity
Muhammad Shoaib, Adnan Ahmad Ansari, Farhan Haq, Sung Min Ahn
Article
Gastroenterology & Hepatology
Youn I. Choi, Jun-won Chung, Kyoung Oh Kim, Kwang An Kwon, Yoon Jae Kim, Dong Kyun Park, Sung Min Ahn, So Hyun Park, Sun Jin Sym, Dong Bok Shin, Young Saing Kim, Ki Hoon Sung, Jeong-Heum Baek, Uhn Lee
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2019)
Article
Biology
Farhan Haq, Salmaan Sharif, Adnan Khurshid, Aamer Ikram, Imran Shabbir, Muhammad Salman, Abdul Ahad, Muhammad Suleman Rana, Aroosha Raja, Nazish Badar, Hanaa Tashkandi, Turki Al Amri, Esam Azhar, Mohammed S. Almuhayawi, Steve Harakeh, Muhammad Faraz Arshad Malik
Summary: The sudden outbreak of COVID-19 has presented challenges to global health systems, with the need for rapid and reliable detection of SARS-CoV-2. The RT-LAMP assay has been validated as a potential alternative for COVID-19 detection, showing high sensitivity and specificity without the need for expensive instruments.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Ji-Yon Shin, Sung-Min Ahn
Summary: The study found that Src plays a crucial role in the endosomal delivery of the FGFR4 signaling complex in HCC. This provides a scientific rationale for repurposing Src inhibitors for the treatment of HCCs with activated FGFR4 pathway.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Aroosha Raja, Muhammad Faraz Arshad Malik, Farhan Haq
Summary: The study identified that dysregulation of six genes in FGFs and IGF pathways in PDAC were significantly associated with clinical characteristics and overall survival. Overexpression of FGF14 was specifically linked to better overall survival in all three cohorts, making it a potential independent prognostic marker. FMN2 and PGR were identified as top genes correlated with FGF14, suggesting their potential as prognostic markers and new therapeutic targets in PDAC.
Review
Oncology
Aroosha Raja, Farhan Haq
Summary: This review extensively summarizes current information on molecular classification of HCC, providing insight for understanding the development mechanisms and treatment options for liver cancer patients globally.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Biochemical Research Methods
Amir Khan, Ji-Yon Shin, Min Kyung So, Jung-Hyun Na, Sune Justesen, Adnan Ahmad Ansari, Byoung Joon Ko, Sung-Min Ahn
Summary: This study aimed to characterize the peptidome that binds to HLA-A*33:03, identifying 5731 unique peptides associated with this allele and experimentally validating the affinity and stability of 40 peptides. It represents the largest dataset of peptides linked to HLA-A*33:03 and the first experimental validation of HLA A*33:03-associated peptides.
Article
Health Care Sciences & Services
Fomaz Tariq, Walizeb Khan, Washaakh Ahmad, Syeda Kiran Riaz, Mahvish Khan, Subuhi Sherwani, Shafiul Haque, Muhammad Faraz Arshad Malik, Muhammad Jahangir Iftikhar, Saif Khan, Farhan Haq
Summary: The study investigated how HLAs modulate HCC development at the transcriptomic level, identifying a set of seven genes as predictors of delayed recurrence. The co-expression of these genes may lead to improved patient prognosis. Further studies are needed for consideration in clinical practice.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Medicine, General & Internal
Walizeb Khan, Washaakh Ahmad, Anwar M. Hashem, Shadi Zakai, Shafiul Haque, Muhammad Faraz Arshad Malik, Steve Harakeh, Farhan Haq
Summary: The Fibroblast Growth Factor Receptors (FGFRs) have been found to regulate cancer metabolism in hepatocellular carcinoma (HCC) and are clinically relevant in HCV-positive HCC cases. The study revealed that FGFR1 was upregulated in HCV+ HCC patients in vitro, but downregulated in all three independent HCC cohorts. On the other hand, FGFR2 was overexpressed in both in vitro and HCC cohorts, and showed a strong correlation between cirrhosis and HCV in all four HCC cohorts. Based on these findings, FGFR2 expression can be used to classify HCC patients based on HCV infection, potentially leading to new therapeutic strategies for HCV-positive HCC subtypes.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Genetics & Heredity
Aroosha Raja, Jonas J. W. Kuiper
Summary: This review discusses the genetic regulation and diversity of endoplasmic reticulum aminopeptidase 2 (ERAP2) in human evolution. The highly polymorphic ERAP2 gene encodes haplotypes that confer resistance against infectious diseases, but also increase the risk for autoimmune disorders. Additionally, the presence of Neanderthal DNA sequences in ERAP2 of modern humans, as well as the impact of human adaptation and historic pandemics on the susceptibility to infectious and inflammatory diseases today, are highlighted.
GENES AND IMMUNITY
(2023)
