Polymerase proofreading domain mutations: New opportunities for immunotherapy in hypermutated colorectal cancer beyond MMR deficiency.
Crit Rev Oncol Hematol
; 113: 242-248, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28427513
ABSTRACT
Immune checkpoint inhibition is a new therapeutic strategy that has shown promising efficacy in many cancer types. Significant activity associated with mismatch repair (MMR) deficiency has been observed in hypermutated, microsatellite unstable (MSI) metastatic colorectal cancer (CRC). Beyond deficient-MMR tumors, somatic or germline DNA polymerase D1 (POLD1) or DNA polymerase E (POLE) alterations cause a hypermutated phenotype in CRC. This recently identified and rare subgroup of proficient-MMR tumors may also benefit from immunotherapy. In this review, we provide a comprehensive overview of recent data on CRC tumors harboring POLD1 or POLE mutations, with a focus on their molecular, histological, and clinical features. We also examine the evidence supporting the development of immune checkpoint inhibitors in this specific subgroup of CRC patients.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndromes Neoplásicas Hereditárias
/
Neoplasias Encefálicas
/
Neoplasias Colorretais
/
DNA Polimerase II
/
DNA Polimerase III
/
Mutação
Tipo de estudo:
Etiology_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article