Yulia Glick Gorman
A5045315512- PARP inhibition in cancer therapy
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Diet, Metabolism, and Disease
- Pancreatic function and diabetes
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Lung Cancer Treatments and Mutations
- Pancreatitis Pathology and Treatment
- Biochemical and Molecular Research
- Renal cell carcinoma treatment
Sheba Medical Center
2018-2023
Tel Aviv University
2019-2021
Germline BRCA-associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum response platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable followed by acquired resistance (OS <36 months), (iii) long-term responders >36 months). Patient-derived xenografts (PDX) generated from 25 at different time points. Response...
Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than 1 year, underscoring the importance evaluating novel targets matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on pro-oncogenic mRNA stability factor HuR (
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA ‐associated PDAC comprises a clinically relevant subtype. A portion these patients are highly susceptible to DNA damaging therapeutics, however, responses heterogeneous and clinical resistance evolves. We have developed unique patient‐derived xenograft (PDX) models from metastatic lesions germline ‐mutated obtained at distinct time points; before treatment progression. Thus, closely mimicking scenarios,...
<p>Supplementary Figure S1 describes mRNA and protein expression of PARG in shPARG models vitro sensitivity to oxaliplatin.</p>
<p>Supplementary Table 1 describes BRCA and KRAS status of PDX models IC50 PDDX-001 olaparib in PDAC/PDX lines</p>
<p>Supplementary Figure S3 describes synthetic lethality of olaparib with siDDR in PDAC.</p>
<p>Supplementary Fig S2 describes protein expression of PARG across PDAC cell models and drug sensitivity PDAC, KPC, DLD RKO cells to olaparib and/or PDDX-001.</p>
<p>Supplementary Fig S7 describes western blot and RTPCR of PARG in modified shPARG cells.</p>
<p>Supplementary Figure S6 describes cleaved caspase 3 expression and quantitation of H2AX foci in MIA PaCa-2 after combination PDDX-001 oxaliplatin.</p>
<p>Supplementary Fig S4 describes synergy plots in Hs 766T cells.</p>
<p>Supplementary Figure S5 describes PARG ELISA.</p>
<div>Abstract<p>Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than 1 year, underscoring the importance evaluating novel targets matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on pro-oncogenic mRNA stability factor HuR (<i>ELAVL1</i>). Here, we evaluated PARG as in PDAC models using both genetic silencing and established...
<p>Supplementary Fig S4 describes synergy plots in Hs 766T cells.</p>
<p>Supplementary Figure S3 describes synthetic lethality of olaparib with siDDR in PDAC.</p>
<p>Supplementary Table 1 describes BRCA and KRAS status of PDX models IC50 PDDX-001 olaparib in PDAC/PDX lines</p>
<p>Supplementary Figure S1 describes mRNA and protein expression of PARG in shPARG models vitro sensitivity to oxaliplatin.</p>
<p>Supplementary Figure S5 describes PARG ELISA.</p>
<p>Supplementary Fig S7 describes western blot and RTPCR of PARG in modified shPARG cells.</p>
<p>Supplementary Fig S2 describes protein expression of PARG across PDAC cell models and drug sensitivity PDAC, KPC, DLD RKO cells to olaparib and/or PDDX-001.</p>
<p>Supplementary Figure S6 describes cleaved caspase 3 expression and quantitation of H2AX foci in MIA PaCa-2 after combination PDDX-001 oxaliplatin.</p>
<p>Mechanisms of resistance in glBRCA PDAC</p>
<div>Abstract<p>Germline <i>BRCA</i>–associated pancreatic ductal adenocarcinoma (gl<i>BRCA</i> PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with gl<i>BRCA</i> PDAC were stratified based on the spectrum response platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable followed by acquired resistance (OS <36 months), (iii) long-term responders >36...