Thiosemicarbazones reprogram pancreatic cancer bidirectional oncogenic signaling between cancer cells and stellate cells to suppress desmoplasia.
Future Med Chem
; 14(13): 1005-1017, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35670251
ABSTRACT
Standard treatments have shown dismal activity against pancreatic cancer (PC), due in part to the development of a dense stroma (desmoplasia). This perspective discusses the development of the di-2-pyridylketone thiosemicarbazones that overcomes bidirectional oncogenic signaling between PC cells and pancreatic stellate cells (PSCs), which is critical for desmoplasia development. This activity is induced by the up-regulation of the metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1), which inhibits oncogenic signaling via HGF, IGF-1 and Sonic Hedgehog pathway. More recent studies have deciphered additional pathways including those mediated by Wnt and tenascin C that are secreted by PSCs to activate ß-catenin and YAP/TAZ signaling in PC cells. Suppression of bidirectional signaling between cell types presents a unique therapeutic opportunity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Thiosemicarbazones
Limits:
Humans
Language:
En
Journal:
Future Med Chem
Year:
2022
Document type:
Article
Affiliation country: