Kai Yu Jen
A5042279631- Fibroblast Growth Factor Research
- Eosinophilic Disorders and Syndromes
- Kruppel-like factors research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Protein Tyrosine Phosphatases
- Epigenetics and DNA Methylation
- Metastasis and carcinoma case studies
- Ubiquitin and proteasome pathways
- Asthma and respiratory diseases
- Immune Response and Inflammation
- PI3K/AKT/mTOR signaling in cancer
- Biochemical and Molecular Research
- Immune Cell Function and Interaction
- Oral and Maxillofacial Pathology
- Peptidase Inhibition and Analysis
- Neonatal Respiratory Health Research
- Gut microbiota and health
- Lung Cancer Treatments and Mutations
- Advanced Breast Cancer Therapies
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Enzyme function and inhibition
- Proteoglycans and glycosaminoglycans research
- Oral Health Pathology and Treatment
- Nicotinic Acetylcholine Receptors Study
Relay Therapeutics (United States)
2021-2024
Sage Therapeutics (United States)
2021-2023
Niigata University
2005-2012
University of California, San Diego
2007-2008
Abstract Oncogenic activation of fibroblast growth factor receptor 2 (FGFR2) drives multiple cancers and represents a broad therapeutic opportunity, yet selective targeting FGFR2 has not been achieved. Although the clinical efficacy pan-FGFR inhibitors (pan-FGFRi) validates driver status in fusion–positive intrahepatic cholangiocarcinoma, their benefit is limited by incomplete target coverage due to FGFR1- FGFR4-mediated toxicities (hyperphosphatemia diarrhea, respectively) emergence...
<p>Supplementary Tables</p>
<div>Abstract<p>Src homology-2 domain–containing phosphatase 2 promotes rat sarcoma viral oncogene homolog–MAPK signaling and tumorigenesis is a promising therapeutic target for multiple solid tumors. Migoprotafib potent highly selective Src inhibitor designed the treatment of homolog–MAPK–driven cancers, particularly in combination with other targeted agents. Here, we report first-in-human study results single-agent migoprotafib patients advanced tumor. We conducted phase Ia,...
Background: One of the histologic characteristics epithelial dysplasias oral mucosa is droplet‐shaped rete processes resulting from a solid proliferation basaloid cells. These cells are suddenly changed into an overlay parakeratotic However, it unknown how this characteristic two‐phase appearance generated. Methods: Formalin‐fixed paraffin sections mucosal specimens with normal, hyperplastic, dysplastic epithelia and squamous cell carcinomas were examined for apoptosis by terminal...
Abstract Background: Oncogenic FGFR2 alterations (fusions/rearrangements [f/r], amplifications, mutations) drive multiple solid tumors. Pan-FGFR inhibitors have validated as an actionable target in cholangiocarcinoma (CCA), however, activity has been limited by off-isoform toxicity and on-target resistance. Lirafugratinib (RLY-4008), the first highly selective inhibitor, was studied ReFocus, ongoing Phase I/II study (NCT04526106) advanced FGFR2-altered tumor patients (pts). Previously, we...
Abstract CD45, a type I transmembrane protein tyrosine phosphatase expressed on nucleated hemopoietic cells, is prominently involved in T cell activation. Ligation of CD45RB isoforms has been associated with transplant tolerance. A recent genotyping analysis asthma indicates correlation CD45 splicing. In this study, we administered an anti-CD45RB mAb (aCD45) murine model allergic and found that ligation decreases responses. aCD45 allergen-induced pulmonary eosinophilia, bronchoalveolar...
TPS4165 Background: Oncogenic activation of FGFR2 via genomic rearrangement, gene amplification, or point mutation in advanced solid tumors provides the opportunity for rapid clinical development highly selective inhibitors using a precision oncology approach to deliver benefit genomically-defined patient (pt) populations. Unfortunately, this remains largely unrealized as current, non-selective small molecule (pan-FGFRi) suffer from off-isoform toxicity (FGFR1-hyperphosphatemia;...
Abstract INTRODUCTION: Oncogenic FGFR2 alterations (fusions/rearrangements, amplifications, mutations) are key drivers in cholangiocarcinoma (CCA) and multiple solid tumors. Current pan-FGFR inhibitor (FGFRi) therapy is limited by off-isoform toxicity acquired kinase domain resistance mutations. RLY-4008 a highly selective potent oral designed to target both driver We initiated first-in-human study advanced tumors patients (pts) define the safety, pharmacokinetics (PK) efficacy of...
TPS1124 Background: Targeting constitutively active mutant kinases with selective small molecule inhibitors is a key therapeutic pillar of precision oncology. Phosphatidylinositol-4,5bisphosphate-3 kinase, catalytic subunit alpha ( PIK3CA) mutations leading to oncogenic activation PI3Kα represent the largest opportunity for this approach in solid tumors. However, there no inhibitor that targets clinic. Toxicity related non-selective inhibition WT (hyperglycemia) and other PI3K isoforms...
<p>ReFocus entry criteria</p>
<p>ReFocus entry criteria</p>
<p>three references cited in supplementary data</p>
<p>Supplementary Figure 1. RLY-4008 is an irreversible inhibitor of FGFR2.</p>
<p>Supplementary Figure 1. RLY-4008 is an irreversible inhibitor of FGFR2.</p>
<p>Supplementary Figure 2. Treatment with RLY-4008 is well-tolerated and leads to dose-dependent inhibition of FGFR2 tumor regression in multiple FGFR2-altered models.</p>
<div>Abstract<p>Oncogenic activation of fibroblast growth factor receptor 2 (FGFR2) drives multiple cancers and represents a broad therapeutic opportunity, yet selective targeting FGFR2 has not been achieved. While the clinical efficacy pan-FGFR inhibitors (pan-FGFRi) validates driver status in fusion-positive intrahepatic cholangiocarcinoma, their benefit is limited by incomplete target coverage due to FGFR1- FGFR4-mediated toxicities (hyperphosphatemia diarrhea) emergence...
<p>Supplementary Figure 2. Treatment with RLY-4008 is well-tolerated and leads to dose-dependent inhibition of FGFR2 tumor regression in multiple FGFR2-altered models.</p>
<p>three references cited in supplementary data</p>