Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm.
Cancers (Basel)
; 15(15)2023 Jul 28.
Article
en En
| MEDLINE
| ID: mdl-37568648
Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers. Recently, several clinical trials have utilized ICIs as potential neoadjuvant therapies for MSI-H gastrointestinal cancers and demonstrated deep clinical and pathological responses, creating opportunities for organ preservation. However, there are potential challenges to the neoadjuvant use of ICIs for certain disease types due to the clinical risk of overtreatment for a disease that can be cured through a surgery-only approach. In this review article, we discuss neoadjuvant management approaches with ICI therapy for patients with MSI-H gastrointestinal cancers, including those with oligometastatic disease. We also elaborate on potential challenges and opportunities for the neoadjuvant utilization of ICIs and provide further insight into the changing treatment paradigm of MMR-D/MSI-H gastrointestinal cancers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Cancers (Basel)
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Suiza