Erdafitinib

PURPOSE: Despite fibroblast growth factor receptor ( FGFR ) inhibitors being approved in tumor types with select FGFR rearrangements or gene mutations, amplifications of FGFR represent the most common FGFR alteration across malignancies. Subprotocol K1 (EAY131-K1) of the National Cancer Institute-MATCH platform trial was designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 amplification. METHODS: EAY131-K1 was an open-label, single-arm, phase II study with central confirmation of presence of FGFR1-4 amplification in tumors...

PURPOSE: Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions. METHODS: Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded. Enrolled subjects received oral erdafitinib at a starting dose of 8 mg daily continuously until intolerable toxicity or disease progression...

No abstract text is available yet for this article.

PURPOSE: This report aims to highlight the wide spectrum of ophthalmic adverse events associated with erdafitinib, a fibroblast growth factor inhibitor that blocks activation of the mitogen-activated protein kinase kinase (MAPK/MEK) cascade. The purpose of this report is to describe a case of erdafitinib-associated bilateral outer retinal alterations in the MEK-associated retinopathy spectrum and rapid onset bilateral total cataracts following a 20-month course of erdafitinib therapy...

The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

The successful fabrication is reported of highly crystalline Co nanoparticles interconnected with zeolitic imidazolate framework (ZIF-12) -based amorphous porous carbon using the molten-salt-assisted approach utilizing NaCl. Single crystal diffractometers (XRD), and X-ray photoelectron spectroscopy (XPS) analyses confirm the codoped amorphous carbon structure. Crystallite size was calculated by Scherrer (34 nm) and Williamson-Hall models (42 nm). The magnetic properties of NPCS (N-doped porous carbon sheet) were studied using a vibrating sample magnetometer (VSM)...

As frontline treatment of advanced urothelial cancer (UC) evolves, optimal sequencing of subsequent therapies remains unclear. The phase 3 THOR trial compared the efficacy of erdafitinib to chemotherapy or immunotherapy in FGFR3/2-altered advanced UC. THOR offers valuable data informing sequencing strategies, reinforcing the need for molecular testing in UC.

The biochemical basis for substrate dependences in apparent inhibition constant values ( K i ) remains unknown. Our study aims to elucidate plausible structural determinants underpinning these observations. In vitro steady-state inhibition assays conducted using human recombinant CYP3A4 enzyme and testosterone substrate revealed that fibroblast growth factor receptor (FGFR) inhibitors erdafitinib and pemigatinib noncompetitively inhibited CYP3A4 with apparent K i values of 10.2 ± 1.1 and 3.3 ± 0.9 μM, respectively...

Cancer aggressiveness has been linked with obesity, and studies have shown that adipose tissue can enhance cancer progression. In this issue of Cancer Research, Hosni and colleagues discover a paracrine mechanism mediated by adipocyte precursor cells through which urothelial carcinomas become resistant to erdafitinib, a recently approved therapy inhibiting fibroblast growth factor receptors (FGFR). They identified neuregulin 1 (NRG1) secreted by adipocyte precursor cells as an activator of HER3 signaling that enables resistance...

Fibroblast growth factor (FGF) signalling via FGF receptors (FGFR1-4) orchestrates fetal development and contributes to tissue and whole-body homeostasis, but can also promote tumorigenesis. Various agents, including pan-FGFR inhibitors (erdafitinib and futibatinib), FGFR1/2/3 inhibitors (infigratinib and pemigatinib), as well as a range of more-specific agents, have been developed and several have entered clinical use. Erdafitinib is approved for patients with urothelial carcinoma harbouring FGFR2/3 alterations, and futibatinib and pemigatinib are approved for patients with cholangiocarcinoma harbouring FGFR2 fusions and/or rearrangements...

The integration of pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations with artificial intelligence/machine learning algorithms is one of the most attractive areas of the pharmacometric research. These hybrid techniques are currently under investigation to perform several tasks, among which precision dosing. In this scenario, this paper presents and evaluates a new framework embedding PK-PD models into a reinforcement learning (RL) algorithm, Q-learning (QL), to personalize pharmacological treatment...

Bladder cancer is the tenth most common cancer and is a significant burden on health care services worldwide, as it is one of the most costly cancers to treat per patient. This expense is due to the extensive treatment and follow-ups that occur with costly and invasive procedures. Improvement in both treatment options and the quality of life these interventions offer has not progressed at the rates of other cancers, and new alternatives are desperately needed to ease the burden. A more modern approach needs to be taken, with urinary biomarkers being a positive step in making treatments more patient-friendly, but there is still a long way to go to make these widely available and of a comparable standard to the current treatment options...

New drugs being established in the market every year produce specified structures for selective biological targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56 drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib, Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib, Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib, Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib, Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68 PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin, Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin, Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin, Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived asparaginase) approved by the U...

OBJECTIVE: This study aims at revealing the relationship between S100A11 and cancer-associated fibroblasts (CAFs) in prostate cancer and improving T cell infiltration into solid tumors. METHODS: H&E, IHC and Sirius red staining were used to detect the stroma content in prostate cancer tissues. Stable S100A11 knockdown cell lines DU 145, 22Rv1, RM-1 and NOR-10 were established by lentivirus transfection. Co-culture system of RM-1 and CAFs was established. CCK-8, wound healing and transwell were proceeded to determine proliferation, migration and invasion of prostate cancer cells...

The combination of targeted therapy with immune checkpoint inhibition (ICI) is an area of intense interest. We studied the interaction of fibroblast growth factor receptor (FGFR) inhibition with ICI in urothelial carcinoma (UC) of the bladder, in which FGFR3 is altered in 50% of cases. Using an FGFR3-driven, Trp53-mutant genetically engineered murine model (UPFL), we demonstrate that UPFL tumors recapitulate the histology and molecular subtype of their FGFR3-altered human counterparts. Additionally, UPFL1 allografts exhibit hyperprogression to ICI associated with an expansion of T regulatory cells (Tregs)...

Alterations of the fibroblast growth factor (FGF) signalling pathway are increasingly recognized as frequent oncogenic drivers of paediatric brain tumours. We report on three patients treated with the selective FGFR1-4 inhibitor erdafitinib. Two patients were diagnosed with a posterior fossa ependymoma group A (PFA EPN) and one with a low-grade glioma (LGG), harbouring FGFR3/FGFR1 overexpression and an FGFR1 internal tandem duplication (ITD), respectively. While both EPN patients did not respond to erdafitinib treatment, the FGFR1-ITD-harbouring tumour showed a significant decrease in tumour volume and contrast enhancement throughout treatment...

Aberrations of the fibroblast growth factor receptor (FGFR) family members are frequently observed in metastatic urothelial cancer (mUC), and blocking the FGF/FGFR signaling axis is used as a targeted therapeutic strategy for treating patients. Erdafitinib is a pan-FGFR inhibitor that has recently been approved by the Food and Drug Administration for mUC with FGFR2/3 alterations. Although mUC patients show initial response to erdafitinib, acquired resistance rapidly develops. Here, we found that adipocyte precursors promoted resistance to erdafitinib in FGFR-dependent bladder and lung cancer in a paracrine manner...

The crucial role of cancer-associated fibroblasts (CAFs) in promoting T-cell exclusion has a significant impact on tumor immune evasion and resistance to immunotherapy. Therefore, enhancing T-cell infiltration into solid tumors has emerged as a pivotal area of research. We achieved a conventional knockout of Shcbp1 (Shcbp1-/- ) through CRISPR/Cas9 gene editing and crossed these mice with spontaneous breast cancer MMTV-PyMT mice, resulting in PyMT Shcbp1-/- mice. The different CAF subtypes were detected by flow cytometry analysis (FCA)...