Kamil Bruderek
A5075997095- Fibroblast Growth Factor Research
- Eosinophilic Disorders and Syndromes
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
Relay Therapeutics (United States)
2023-2024
Sage Therapeutics (United States)
2021
Constellation Pharmaceuticals (United States)
2020
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...
Fibroblast growth factor receptor (FGFR) kinase inhibitors have been shown to be effective in the treatment of intrahepatic cholangiocarcinoma and other advanced solid tumors harboring FGFR2 alterations, but toxicity these drugs frequently leads dose reduction or interruption such that maximum efficacy cannot achieved. The most common adverse effects are hyperphosphatemia caused by FGFR1 inhibition diarrhea due FGFR4 inhibition, as current therapies not selective among FGFRs. Designing has...
Histone methyltransferase EZH2, which is the catalytic subunit of PRC2 complex, catalyzes methylation histone H3K27—a transcriptionally repressive post-translational modification (PTM). EZH2 commonly mutated in hematologic malignancies and frequently overexpressed solid tumors, where its expression level often correlates with poor prognosis. First generation inhibitors are beginning to show clinical benefit, we believe that a second inhibitor could further build upon this foundation fully...
Abstract FGFR2 fusions, amplifications, and mutations are oncogenic drivers that occur across multiple tumor types. Clinical efficacy observed with pan-FGFR inhibitors has validated the driver status of in fusion-positive intrahepatic cholangiocarcinoma (ICC), however, FGFR1-mediated toxicities (hyperphosphatemia, tissue mineralization) emergence on-target resistance limit inhibitors. To overcome these limitations, we designed RLY-4008, a potent highly selective, inhibitor. Despite...
<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. Although the clinical efficacy pan-FGFR inhibitors (pan-FGFRi) validates <i>FGFR2</i> driver status in fusion–positive intrahepatic cholangiocarcinoma, their benefit is limited by incomplete target coverage due to FGFR1- FGFR4-mediated toxicities...
<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>
<p>Supplementary video legend describing schematic of P-loop dynamics</p>
<p>Supplementary video legend describing schematic of P-loop dynamics</p>