TY - JOUR
T1 - Patient-derived xenograft models of BRCA-associated pancreatic cancers
AU - Golan, Talia
AU - Atias, Dikla
AU - Stossel, Chani
AU - Raitses-Gurevich, Maria
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/4
Y1 - 2021/4
N2 - Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease. The majority of patients diagnosed at an advanced, metastatic stage, and poor overall survival rates. The most clinically meaningful subtype obtained from PDAC genomic classification is represented by unstable genomes, and co-segregated with inactivation of DNA damage repair genes, e.g., Breast cancer 1/2 (BRCA1/2). The FDA and EMA has recently approved olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, as a maintenance strategy for platinum-sensitive advanced PDAC patients with BRCA mutations. However, susceptibility to treatment varies, and resistance may develop. Resistance can be defined as innate or acquired resistance to platinum/PARP-inhibition. Patient-derived xenograft (PDX) models have been utilized in cancer research for many years. We generated a unique PDX model, obtained from BRCA-associated PDAC patients at distinct time points of the disease recapitulating the different clinical scenario. In this review we discuss the relevant PDX-derived models for investigating BRCA-associated PDAC and drug development.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease. The majority of patients diagnosed at an advanced, metastatic stage, and poor overall survival rates. The most clinically meaningful subtype obtained from PDAC genomic classification is represented by unstable genomes, and co-segregated with inactivation of DNA damage repair genes, e.g., Breast cancer 1/2 (BRCA1/2). The FDA and EMA has recently approved olaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor, as a maintenance strategy for platinum-sensitive advanced PDAC patients with BRCA mutations. However, susceptibility to treatment varies, and resistance may develop. Resistance can be defined as innate or acquired resistance to platinum/PARP-inhibition. Patient-derived xenograft (PDX) models have been utilized in cancer research for many years. We generated a unique PDX model, obtained from BRCA-associated PDAC patients at distinct time points of the disease recapitulating the different clinical scenario. In this review we discuss the relevant PDX-derived models for investigating BRCA-associated PDAC and drug development.
KW - BRCA 1/2
KW - Drug development
KW - PARP inhibitors
KW - PDX models
KW - Pancreatic ductal adenocarcinoma
KW - Platinum agents
KW - Resistance
KW - Response
UR - http://www.scopus.com/inward/record.url?scp=85101536187&partnerID=8YFLogxK
U2 - 10.1016/j.addr.2021.02.010
DO - 10.1016/j.addr.2021.02.010
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C2 - 33617901
AN - SCOPUS:85101536187
SN - 0169-409X
VL - 171
SP - 257
EP - 265
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
ER -