fexagratinib (ABSK091) / AstraZeneca, Abbisko - LARVOL DELTA

Deciphering N7-methylguanosine-driven immune dysregulation in unexplained recurrent spontaneous abortion based on transcriptome data and experimental validation. (PubMed, Eur J Med Res) - "This study establishes m7G methylation as a novel epigenetic driver of immune dysregulation in URSA. The predictive signature offers translational tool for risk stratification and targeted therapy, bridging RNA epigenetics with reproductive immunology."

Journal • E2F1 • GATA2 • LSM1 • MIR27A • NCBP2

Ex Vivo Drug Sensitivity Evaluation of a ZMYM2: : FGFR1 Fusion-Positive 8p11 Myeloproliferative Syndrome (EMS) Leukemia (ASH 2023) - "Bortezomib and Axitinib exhibited high efficacy on the patient's sample...Other FGFR inhibitors, including Olverematinib, AZD4547, Axitinib, Cediranib, Dovitinib, and Lenvatinib, also demonstrated exquisite sensitivity. Despite extensive screening, no other single agents or drug combinations exhibited increased effectiveness in the ZMYM2: : FGFR1 transformed BaF3 cells except for Trametinib, a MEK inhibitor, and the combination of Belvarafenib (RAF inhibitor) and Gilteritinib (FLT3 inhibitor)... Ex vivo drug sensitivity assays demonstrated the highly selective efficacy of FGFR inhibitors in ZMYM2: : FGFR1 fusion-positive leukemia cells and a fusion-expressing BaF3 cell line. Mutations in the FGFR1 kinase domain (ZMYM2: : FGFR1 F1171L) could contribute to Ponatinib insensitivity. These ex vivo drug screening results provide further support for ongoing clinical trials which are investigating the use of single agent Pemigatinib and other FGFR1 inhibitors for the..."

Preclinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • FGFR1 • FLT3 • RUNX1 • ZMYM2

Establishment and characterization of preclinical models of human gynecologic tract carcinosarcomas demonstrates targetable FGFR1 alterations. (PubMed, Transl Oncol) - "These findings demonstrate the utility of patient-derived tumor models in the identification and the functional validation of potentially targetable molecular alterations in preclinical setting."

Journal • Preclinical • Carcinosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer • FGFR1 • TP53

Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities. (PubMed, Cell Death Discov) - "CAFs exhibited broad sensitivity to multikinase inhibitors, with dasatinib, midostaurin, and FGFR inhibitors (AZD4547, erdafitinib) emerging as top stromal-directed candidates. These findings underscore the plasticity of prostate CAFs and reveal actionable vulnerabilities, supporting the development of targeted stromal therapies to disrupt tumor-stroma interactions in PCa."

Heterogeneity • Journal • Preclinical • Genito-urinary Cancer • Immune Modulation • Immunology • Oncology • Prostate Cancer • Solid Tumor • CAFs • CAV1 • STAT3 • SULF1

Fibroblast growth factor receptor 3 (FGFR3) - driven genomic landscape and the impact on clinical outcomes of fexagratinib (Fexa) in Chinese metastatic or unresectable urothelial carcinoma (mUC) (ESMO 2025) - P1b/2 | "Conclusions This study revealed that the genomic landscape of Chinese mUC pts was generally consistent with Western cohorts, but a higher frequency of TP53 alts was observed. Certain baseline alts, particularly in the PI3K–mTOR pathway, e.g. TSC1 and PIK3CA, were associated with clinical outcomes of Fexa treatment, informing the putative resistance mechanisms and guiding combination therapy strategies of FGFR inhibitors in mUC."

Clinical • Clinical data • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FANCA • FGFR3 • HER-2 • KDM6A • KMT2D • MTAP • PIK3CA • TACC3 • TP53 • TSC1

Development of PROTACs for targeted degradation of FGFR3-TACC3 oncofusions (AACR-NCI-EORTC 2025) - "While inhibitors of FGFR kinases, such as erdafitinib and fexagratinib, are the treatment of choice for F3T3-driven cancers, most treated patients do not respond to the drug, suggesting insufficient inhibition of the oncofusion activity. These data suggest that chemically-induced degradation of the F3T3 fusion protein can lead to oncogenic signal ablation sufficiently potent to induce a lethal oncogenic shock and can thus yield more durable responses than FGFR3 kinase inhibitors. KHS-C4 was selected for further evaluation to establish in vivo proof of concept for the PROTAC-based therapeutic strategy against F3T3-driven cancers."

Bladder Cancer • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CRBN • FGFR3 • TACC3 • XIAP

Development and Validation of a 7-eRNA Prognostic Signature for Lung Adenocarcinoma. (PubMed, Biology (Basel)) - "Somatic mutation profiling highlighted TP53 and TTN as frequently mutated genes, while drug sensitivity prediction identified four potential therapeutic agents (including AZD4547 and Nutlin-3a) for high-risk individuals. Collectively, this study constructed a 7-eRNA prognostic model for LUAD, providing a powerful tool for clinical risk assessment and uncovering eRNA-mediated regulatory mechanisms."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TP53 • TTN

Deciphering lactate/lactylation networks in AML: integrated scRNA-seq and transcriptomics reveal functions and prognostic model. (PubMed, BMC Cancer) - "Transcriptomic profiling indicated lactylation-associated immunosuppression (e.g., downregulated CXCL9/10-CXCR3 axis, enrichment of T cell exhaustion markers) and heightened in silico-predicted sensitivity to BCL-2/FGFR inhibitors (ABT-737/AZD4547) in high-risk patients. Collectively, integrated analyses uncovered lactate/lactylation-associated heterogeneity in AML. Our machine learning-based prognostic model predicts survival, therapeutic response, and drug sensitivity, suggesting a potential strategy for precision therapeutics in AML."

Biomarker • IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ARPP19 • BCL2 • CXCL9 • CXCR3 • IFI16

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=6452 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Biomarker • Trial completion date • Trial primary completion date • Bladder Cancer • Brain Cancer • Breast Cancer • Cervical Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hematological Malignancies • Hormone Receptor Positive Breast Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Thyroid Gland Carcinoma • Uterine Cancer • CD4 • MSI

Discovery of a 1H-Pyrazol-3-Amine Derivative as a Novel, Selective, and Orally Available RIPK1 Inhibitor for the Treatment of Inflammatory Disease. (PubMed, J Med Chem) - "Herein, we present the structural optimization and investigation into the structure-activity relationship of a series of 1H-pyrazol-3-amine derivatives, derived from the clinical-stage FGFR inhibitor AZD4547...Furthermore, 44 showed good therapeutic effects in both TNF-α-induced systemic inflammatory response syndrome and DSS-induced inflammatory bowel disease models in vivo. In summary, 44 is a promising lead compound for RIPK1 inhibition and warrants further study."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Systemic Inflammatory Response Syndrome • RIPK1 • TNFA

Fibroblast growth factor-23 remodels vascular extracellular matrix via glycosaminoglycan induction: implications for calcification in chronic kidney disease. (PubMed, Ren Fail) - "Similarly, the FGFR inhibitor AZD4547 abolished FGF-23-induced increases in sGAGs and calcification in both VSMCs and ECs. These findings indicate that FGF-23 modulates vascular GAG composition and promotes calcification, thereby contributing to pathological vascular remodeling in CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • FGF23 • HAS2

Dual-parameter tomographic imaging of attenuation and backscattering coefficients for quantitative evaluation of immune cell-mediated cytotoxicity in tumor spheroids. (PubMed, Theranostics) - "This approach enables high-resolution measurements of structural and optical property changes associated with apoptosis, allowing spatial and temporal mapping of treatment-induced cytotoxicity in HER2-positive breast tumor spheroids treated with AZD4547 and HER2-targeted chimeric antigen receptor (CAR) T cells... This dual-parameter OCT-based assay framework provides a sensitive, label-free method for distinguishing between immune- and drug-induced apoptosis in tumor spheroids. Its strong correlation with viability and capacity to resolve spatially resolved dynamics underscore its potential for robust, in situ assessment of immunotherapeutic efficacy."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Integrative Transcriptomic-Histological Analysis in Dilated Cardiomyopathy Unveils FGFR1 Inhibition as Anti-Cardiac Fibrotic and Cardioprotective Therapy. (PubMed, JACC Basic Transl Sci) - "FGFR1 expression correlated with fibrosis severity, and inhibition by AZD4547 reduced fibrosis and improved cardiac function in organoid and murine models. These findings validate FGFR1 inhibition as a promising therapeutic strategy for mitigating fibrosis and improving outcomes in heart failure associated with DCM."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

Synergistic Anticancer Effects of Fibroblast Growth Factor Receptor Inhibitor and Cannabidiol in Colorectal Cancer. (PubMed, Nutrients) - "The combination of FGFR inhibitors and cannabidiol exhibited a synergistic effect in inducing cell death in colorectal cancer cells, likely through the ER stress pathway. This study supports the potential of combined FGFR inhibitor and CBD therapy as a promising strategy for enhancing anticancer effects in CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ANXA5 • FGFR • FGFR2

Targeting p-FGFR1Y654 Enhances CD8+ T Cells Infiltration and Overcomes Immunotherapy Resistance in Esophageal Squamous Cell Carcinoma by Regulating the CXCL8-CXCR2 Axis. (PubMed, Biomedicines) - "AZD4547, combined with immunotherapy, further promotes immunotherapeutic efficacy in ESCC. In conclusion, our study presents a promising model for combination therapy in ESCC immunotherapy."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • CXCL8 • CXCR2

PANoptosis-driven molecular stratification in esophageal squamous cell carcinoma: A multi-omics prognostic model and FGFR-Targeted therapeutic validation. (PubMed, Comput Biol Med) - "This study developed and validated the first prognostic model for ESCC based on PANoptosis, highlighting FGFR inhibitors as potential therapeutic strategies for targeting specific subtypes through the suppression of EMT and modulation of the MYC/E2F pathways."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • CCNE1 • CEACAM1 • CRYAB • ERBB3 • FGFR • KLF5 • MAPK13 • PLAU

FGFR1 overexpression promotes resistance to PI3K inhibitor alpelisib in luminal breast cancer cells through receptor tyrosine kinase signaling-mediated activation of the estrogen receptor. (PubMed, Cancer Drug Resist) - "Synergistic effects of alpelisib with AZD4547 and fulvestrant were evaluated using the combination index. Our findings establish FGFR1 as a key mediator of alpelisib resistance in ER+ breast cancer. Combining FGFR1 inhibitors with alpelisib-based therapies offers a viable approach for FGFR1-overexpressing tumors."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • FGFR1

High Dietary Phosphate Intake Induces Hypertension and Sympathetic Overactivation Through Central Fibroblast Growth Factor Receptor Signaling. (PubMed, Circulation) - "ICV injection of BLU9931, a relatively selective FGFR4 inhibitor, also decreased the responses in HP rats only (∆RSNA=112±70 versus 65±46% [P=0.006] and ∆MAP=41±14 versus 20±14 mm Hg [P<0.0001] before versus after ICV injection). However, ICV administration of AZD4547, a FGFR1-3 inhibitor, and C-terminal FGF23 peptide, a competitive inhibitor of FGF23/FGFR/α-Klotho complex formation, did not alter the responses in either NP or HP animals. Our data reveal a novel pathophysiologic paradigm of high-phosphate diet-induced sympathoexcitation and hypertension by FGF23 crossing into the brain, possibly acting through FGFR4."

Journal • Anesthesia • Cardiovascular • Hypertension • FGF23 • FGFR • FGFR4

Dysregulated lipids homeostasis disrupts CHAC1-mediated ferroptosis driving fibroblast growth factor receptor tyrosine kinase inhibitor AZD4547 resistance in gastric cancer. (PubMed, Redox Biol) - "Dysregulated lipid homeostasis downregulated CHAC1-mediated ferroptosis, leading to FGFR-TKI resistance in gastric cancer. Overexpression of CHAC1 or inhibiting cholesterol synthesis presents promising therapeutic strategies to overcome FGFR-TKI resistance in GC."

Journal • Gastric Cancer • Metabolic Disorders • Oncology • Solid Tumor • CHAC1 • FGFR

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=423 | Active, not recruiting | Sponsor: University of Birmingham | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • NKX2-1 • TP63

Targeting FGFR Attenuates Tumor Growth in an Anal Squamous Cell Carcinoma Patient Derived Xenograft Model. (PubMed, Mol Carcinog) - "Fourier-transform infrared (FTIR) spectroscopy of post-treatment residual tumors revealed significant differences in the Amide I and Amide II regions between AZD4547-treated and control groups. These findings demonstrate that FGFR inhibition effectively attenuates ASCC tumor growth and highlights the promise of precision medicine in managing this rare cancer."

Journal • Preclinical • Anal Carcinoma • Oncology • Squamous Cell Carcinoma • CASP3 • FGFR

BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=117 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Jan 2026

Biomarker • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CCNE1 • CDKN2A • HRD • MYCL • MYCN • RB1

Fibroblast growth factor 8 (FGF8) induces mitochondrial remodeling in chondrocytes via ERK/AMPK signaling pathway. (PubMed, FASEB J) - "In contrast, both AZD4547 and U0126 inhibitors abolished mitochondrial elongation as well as the alteration of fusion-fission proteins induced by FGF8, and U0126 also inhibited the FGF8-triggered activation of AMPK. This study is the first to reveal that FGF8 remodels mitochondria through ERK/AMPK signaling in chondrocytes, offering novel insights into the potential role of FGF8 in OA."

Journal • Immunology • Ocular Inflammation • Osteoarthritis • Pain • Rheumatology • FGF8 • FGFR • MFN2 • OPA1

FGFR3 signaling is essential for gastric cancer cell triggering the transition of BM-MSCs into tumor-associated MSCs. (PubMed, Differentiation) - "Suppression of FGFR3 signaling by AZD4547 or siRNA against FGFR3 notably blocked the miR-99a-5p inhibitor-induced BM-MSCs transition and the oncogenic roles of GC-MSCs...Taken together, although manipulating miR-99a-5p to mimic its levels in GC-MSCs promotes the transition of BM-MSCs into GC-MSCs-like cells, FGFR3 signaling, rather than miR-99a-5p, is unexpectedly essential for the education of BM-MSCs by gastric cancer cells. This discovery provides a novel mechanism underlying the transition of BM-MSCs into tumor-associated MSCs and identifies potential therapeutic targets for gastric cancer."

Journal • Gastric Cancer • Oncology • Solid Tumor • FGFR3 • MIR99A

Human-induced pluripotent stem cell-derived exosomes promote skin wound healing through activating FGF2-mediated p38 pathway. (PubMed, Mol Cell Biochem) - "In addition, fibroblast growth factor 2 (FGF-2) was existent in hiPSC-Exos, and hiPSC-Exos could upregulate the p-p38/p38 level, which could be significantly reversed by AZD4547, but not affect the p-ERK/ERK and p-JNK/JNK levels in wound model tissues and cells. In conclusion, hiPSC-Exos may have the potential to promote wound healing by inhibiting cell inflammation as well as promoting cell proliferation and migration based on inherent FGF-2 targeting to FGFR3 to activate p38 pathway, which may serve as a promising candidate for skin healing."

Journal • Inflammation • Mood Disorders • CCL2 • CXCL5 • FGF2 • FGFR3 • IL1B • PCNA