We conducted a phase 2 trial of pan-fibroblast growth factor receptor inhibitor rogaratinib in patients with sarcoma and report here on the cohort of patients with advanced SDH-deficient GIST...This trial illustrates a successful demonstration of targeted cancer therapy predicated on an epigenetic mechanism of oncogene activation. Clinicaltrials.gov identifier: NCT04595747 .

Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.

Compared with Erdafitinib, NP-PE inhibited the expression of FGFR3 to a higher extent. In animal models with bladder cancer, NP-PE inhibited tumor growth, stimulated antitumor immunity, and synergized with antiprogrammed cell death-ligand 1 (aPD-L1), offering a novel approach for the treatment of bladder cancer.

The MDS consistently demonstrated the formation of stable protein-ligand complexes between FGFR3 and Cycloartobiloxanthone/Desoxylimonin throughout the trajectory. Based on these results, it can be inferred that Cycloartobiloxanthone and Desoxylimonin can potentially serve as valuable scaffolds in developing drugs targeting FGFR3 for cancer therapeutic after required validation.

Collaboration between nephrologists and oncologists is crucial for optimizing treatment benefits and managing side effects. Further research is warranted to refine management strategies and to understand the clinical implications of hyperphosphatemia.

Patients who developed cataracts had longer median (range) duration of FGFRi treatment compared with patients who did not develop cataracts (13 months [2-26] vs 5 months [1-11]; odds ratio, 1.01; 95% CI, 1.00-1.02; P = .02). While this retrospective case series study cannot prove cause and effect conclusively due to the study design, study results highlight cataract formation or progression as a potential adverse effect of FGFRi therapy, supporting consideration of periodic eye examinations in patients who have received this treatment.

Molecular docking simulation of 9a in the binding pocket of FGFR-1 confirms its capability to achieve the characteristic interactions of the type II FGFR-1 inhibitors. Exploration of the ADME properties of 9a-p by SwissADME web tool proved their satisfactory physicochemical properties for the discovery of new anticancer hits.

Conventional chemotherapy with gemcitabine and cisplatin for 19 months resulted in progressive disease. Subsequently, a comprehensive genome profile revealed fibroblast growth factor receptor 2 rearrangement, and hence, pemigatinib administration was initiated...Subsequently, the patient underwent conversion surgery, resulting in successful radical resection of the tumor. The patient has been disease-free for 7 months.

"However, limited evidence has been presented to date for the efficacy of futibatinib in patients progressing under treatment with a non-covalent inhibitor. Between January 2021 and April 2023, 14 patients received futibatinib after treatment with the non-covalent FGFR inhibitors pemigatinib (10 patients) or derazantinib (4 patients). Futibatinib was manageable and active in patients with iCCA progressing under a previously non-covalent FGFR2 inhibitor. Randomized controlled trials are needed to determine the optimal therapeutic approach between an upfront treatment with a covalent inhibitor or a sequential strategy starting with a non-covalent inhibitor, followed by a covalent one if disease progresses due to acquired mutations that this could address."

To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics...Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.

FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

For example, AZD4547 and BGJ398 are gradually entering the consumption cycle and are good options as combined treatments. Artificial intelligence and drug repositioning methods can help preselect suitable drug targets more successfully for future inhibition of carcinogenicity.