TY - JOUR
T1 - Exploring the therapeutic potential of focal adhesion kinase inhibition in overcoming chemoresistance in pancreatic ductal adenocarcinoma
AU - Scianò, Fabio
AU - Terrana, Francesca
AU - Pecoraro, Camilla
AU - Parrino, Barbara
AU - Cascioferro, Stella
AU - Diana, Patrizia
AU - Giovannetti, Elisa
AU - Carbone, Daniela
N1 - Publisher Copyright: © 2024 Future Medicine Ltd.. All rights reserved.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related deaths worldwide. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase often overexpressed in PDAC. FAK has been linked to cell migration, survival, proliferation, angiogenesis and adhesion. This review first highlights the chemoresistant nature of PDAC. Second, the role of FAK in PDAC cancer progression and resistance is carefully described. Additionally, it discusses recent developments of FAK inhibitors as valuable drugs in the treatment of PDAC, with a focus on diamine-substituted-2,4-pyrimidine-based compounds, which represent the most potent class of FAK inhibitors in clinical trials for the treatment of PDAC disease. To conclude, relevant computational studies performed on FAK inhibitors are reported to highlight the key structural features required for interaction with the protein, with the aim of optimizing this novel targeted therapy.
AB - Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related deaths worldwide. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase often overexpressed in PDAC. FAK has been linked to cell migration, survival, proliferation, angiogenesis and adhesion. This review first highlights the chemoresistant nature of PDAC. Second, the role of FAK in PDAC cancer progression and resistance is carefully described. Additionally, it discusses recent developments of FAK inhibitors as valuable drugs in the treatment of PDAC, with a focus on diamine-substituted-2,4-pyrimidine-based compounds, which represent the most potent class of FAK inhibitors in clinical trials for the treatment of PDAC disease. To conclude, relevant computational studies performed on FAK inhibitors are reported to highlight the key structural features required for interaction with the protein, with the aim of optimizing this novel targeted therapy.
KW - Diphenylpyrimidines
KW - Drug resistance
KW - FAK inhibitors
KW - Focal adhesion kinase
KW - Pancreatic ductal adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=85184345490&partnerID=8YFLogxK
U2 - 10.4155/fmc-2023-0234
DO - 10.4155/fmc-2023-0234
M3 - Review article
C2 - 38269431
SN - 1756-8919
VL - 16
SP - 271
EP - 289
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 3
ER -