The irreversible pan-HER inhibitor PF00299804 alone or combined with gemcitabine has an antitumor effect in biliary tract cancer cell lines.
Invest New Drugs
; 30(6): 2148-60, 2012 Dec.
Article
in En
| MEDLINE
| ID: mdl-22197904
ABSTRACT
Biliary tract cancer (BTC) is associated with poor survival and unresponsiveness to chemotherapy. Targeted therapies for BTC have been studied, and HER family members are promising therapeutic targets in BTC. In this study, we evaluated the efficacy of PF00299804, an irreversible pan-HER inhibitor, in eight BTC cell lines alone or combined with gemcitabine. PF00299804 potently inhibited the growth of two cell lines (SNU308 and SNU478) out of the eight BTC cell lines as a single agent. PF00299804 blocked HER family and downstream signaling pathways, inducing G1 arrest or apoptosis. Moreover, PF00299804 exerted synergistic effects with gemcitabine in seven of the eight BTC cell lines, possibly through the regulation of the genes involved in the response to gemcitabine, such as TS (thymidylate synthase), RRM1 (ribonucleotide reductase), and MAGEH1, which is negatively correlated with gemcitabine sensitivity. Our results support the need for further study of PF00299804 alone or combined with gemcitabine for the treatment of BTC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Growth Factor
/
Deoxycytidine
/
Quinazolinones
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Invest New Drugs
Year:
2012
Document type:
Article