FGFR Inhibitors: Clinical Activity and Development in the Treatment of Cholangiocarcinoma.
Curr Oncol Rep
; 23(9): 108, 2021 07 16.
Article
en En
| MEDLINE
| ID: mdl-34269915
PURPOSE OF REVIEW: Cholangiocarcinoma is an aggressive cancer with a poor prognosis and limited treatment. Gene sequencing studies have identified genetic alterations in fibroblast growth factor receptor (FGFR) in a significant proportion of cholangiocarcinoma (CCA) patients. This review will discuss the FGFR signaling pathway's role in CCA and highlight the development of therapeutic strategies targeting this pathway. RECENT FINDINGS: The development of highly potent and selective FGFR inhibitors has led to the approval of pemigatinib for FGFR2 fusion or rearranged CCA. Other selective FGFR inhibitors are currently under clinical investigation and show promising activity. Despite encouraging results, the emergence of resistance is inevitable. Studies using circulating tumor DNA and on-treatment tissue biopsies have elucidated underlying mechanisms of intrinsic and acquired resistance. There is a critical need to not only develop more effective compounds, but also innovative sequencing strategies and combinations to overcome resistance to selective FGFR inhibition. Therapeutic development of precision medicine for FGFR-altered CCA is a dynamic process of involving a comprehensive understanding of tumor biology, rational clinical trial design, and therapeutic optimization. Alterations in FGFR represent a valid therapeutic target in CCA and selective FGFR inhibitors are treatment options for this patient population.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Pirroles
/
Neoplasias de los Conductos Biliares
/
Morfolinas
/
Receptores de Factores de Crecimiento de Fibroblastos
/
Colangiocarcinoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Curr Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos