A5103274476- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Bladder and Urothelial Cancer Treatments
- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Renal cell carcinoma treatment
- Pancreatic and Hepatic Oncology Research
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- DNA Repair Mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Radiation Therapy and Dosimetry
- Monoclonal and Polyclonal Antibodies Research
- Multiple Myeloma Research and Treatments
- Optical Coherence Tomography Applications
- AI in cancer detection
- Neuroblastoma Research and Treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- Adenosine and Purinergic Signaling
23andMe (United States)
2024-2025
Stanford University
2013-2022
Stanford Medicine
2020-2021
Cayuga Community College
2012
Texas A&M University
2012
Cornell University
2011
Biochemical Society
2004
University College London
2004
Significance Here we report a fundamental and previously unknown role for the receptor tyrosine kinase AXL as direct hypoxia-inducible transcription factor target driving aggressive phenotype in renal clear cell carcinoma through regulation of SRC proto-oncogene nonreceptor MET kinase. Of therapeutic relevance, demonstrate that inactivation growth arrest-specific 6 (GAS6)/AXL signaling using soluble decoy reversed invasive metastatic (ccRCC) cells. Furthermore, define pathway by which...
Pharmacologic inhibition or knockout of HIF-prolyl hydroxylases in mice reduces morbidity and mortality from radiation-induced gastrointestinal syndrome.
The AXL receptor and its activating ligand, growth arrest–specific 6 (GAS6), are important drivers of metastasis therapeutic resistance in human cancers. Given the critical roles that GAS6 play refractory disease, this signaling axis represents an attractive target for intervention. However, strong picomolar binding affinity between promiscuity small molecule inhibitors represent challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles engineering a...
Loss of the von Hippel-Lindau (VHL) tumor suppressor is a hallmark feature renal clear cell carcinoma. VHL inactivation results in constitutive activation hypoxia-inducible factors (HIFs) HIF-1 and HIF-2 their downstream targets, including proangiogenic VEGF PDGF. However, antiangiogenic agents inhibitors have limited efficacy cancer therapy due to development resistance. Here we employed an innovative computational platform, Mining Synthetic Lethals (MiSL), identify synthetic lethal...
Abstract Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine genes regulated by hypoxia that promote metastasis, we screen fifty inducible for their effects on invasion. In this study, identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as potent regulator of without affecting cell viability. MAFF expression is elevated metastatic breast cancer patients specifically correlated with hypoxic tumors. Combined ChIP-...
Abstract Purpose: Ovarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB), with reported low patient response rates. We found that the ligand PD-L2 is robustly expressed in samples of ovarian cancers and other malignancies exhibiting suboptimal to ICB but not are sensitive. Therefore, we hypothesize can facilitate escape from through incomplete PD-1 signaling pathway. Experimental Design: engineered soluble form receptor (sPD-1) capable binding neutralizing...
Abstract Angiogenesis is a hallmark of cancer that promotes tumor progression and metastasis. However, antiangiogenic agents have limited efficacy in therapy due to the development resistance. In clear cell renal carcinoma (ccRCC), AXL expression associated with resistance poor survival. Here, we establish role for GAS6/AXL signaling promoting angiogenic potential ccRCC cells through regulation plasminogen receptor S100A10. Genetic therapeutic inhibition xenografts reduced vessel density...
<p>Supplemental Figure S1</p>
<p>23ME-00610 treatment exposure and AE summary</p>
<p>Supplemental Figure S3</p>
<p>Supplemental_all tables and figures</p>
<p>Supplemental Figure S2</p>
<p>Patients were scanned and assessed by RECIST v1.1 approximately every 8 weeks. <b>A,</b> Swimmer plot showing the treatment duration BOR for enrolled patients across all dose levels. PD (star), SD (circle), PR (square) is shown. Additional annotations first or death (upward gray triangle), last non-PD assessment (X mark), ongoing (right-facing black triangle) are included. Each color represents cohort/dose level. Eight that initially received doses ≤600 mg had their...
<div>AbstractPurpose:<p>In this phase 1 portion of a first-in-human 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were examine potential correlates efficacy safety.</p>Patients Methods:<p>Eligible (≥18 years) administered intravenously every 3 weeks (Q3W) using an accelerated titration design followed by...
<p>CD200 and CD200R1 expression in participant tumors. <b>A,</b> Representative photomicrographs of H&E, CD200, IHC-stained sections tumor from a patient with well-differentiated neuroendocrine (patient <a href="#fig2" target="_blank">Fig. 2C</a>) whose target lesions shrank 39% baseline assessments. <b>B,</b> Distribution CD200 H-scores CD200R1-positive immune cells (% positive cells) at baseline. Pink data points present the H-score %–positive...
<p>Supplemental Figure S4</p>
<p>Single-dose serum PK and peripheral target engagement for 23ME-00610 in patients with cancer by dose level. Sample size participants evaluable data cohorts: 1,400 mg (<i>N</i> = 8), 600 200 3),60 4), 20 3), 6 1), 2 1). <b>A,</b> Geometric mean geometric SD cycle 1 concentration–time Below limit of quantitation (BLQ) values were set to missing, plotted only if more than half the was quantifiable [greater lower (LLOQ)] not missing. EC<sub>90</sub>...
<p>Baseline patient and disease characteristics</p>
<p>Supplementary Figure S5</p>
<p>Supplementary Figure S4</p>
<p>Supplementary Figure S8</p>
<p>Supplementary Figure S9</p>
<p>Supplementary Figure S6</p>
<p>Characterization of the binding and blocking activity 23ME-01473</p>