Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting
High microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) phenotype is a distinct molecular signature across gastrointestinal cancers characterized by high tumor mutational burden and high neoantigen load. Tumors harboring dMMR are highly immunogenic and heavily infiltrated by immune...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-03-01
|
| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359231162577 |
| _version_ | 1797857518680014848 |
|---|---|
| author | Mélina Boutin Sharlene Gill |
| author_facet | Mélina Boutin Sharlene Gill |
| author_sort | Mélina Boutin |
| collection | DOAJ |
| description | High microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) phenotype is a distinct molecular signature across gastrointestinal cancers characterized by high tumor mutational burden and high neoantigen load. Tumors harboring dMMR are highly immunogenic and heavily infiltrated by immune cells; consequently, they are uniquely vulnerable to therapeutic strategies enhancing immune antitumor response such as checkpoint inhibitors. The MSI-H/dMMR phenotype arose as a powerful predictor of response to immune checkpoint inhibitors with evidence supporting significantly improved outcomes in the metastatic setting. On the other hand, the genomic instability characteristic of MSI-H/dMMR tumors appears to be associated with decreased sensitivity to chemotherapy, and the benefits of standard adjuvant or neoadjuvant chemotherapy approaches in this subtype are being increasingly questioned. Here, we review the prognostic and predictive impact of MMR status in localized gastric and colorectal cancers, and highlight the emerging clinical data incorporating checkpoint inhibitors in the neoadjuvant setting. |
| first_indexed | 2024-04-09T20:57:59Z |
| format | Article |
| id | doaj.art-e01d423c27b8484e9e86a1be02160327 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-04-09T20:57:59Z |
| publishDate | 2023-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-e01d423c27b8484e9e86a1be021603272023-03-29T14:33:48ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592023-03-011510.1177/17588359231162577Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant settingMélina BoutinSharlene GillHigh microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) phenotype is a distinct molecular signature across gastrointestinal cancers characterized by high tumor mutational burden and high neoantigen load. Tumors harboring dMMR are highly immunogenic and heavily infiltrated by immune cells; consequently, they are uniquely vulnerable to therapeutic strategies enhancing immune antitumor response such as checkpoint inhibitors. The MSI-H/dMMR phenotype arose as a powerful predictor of response to immune checkpoint inhibitors with evidence supporting significantly improved outcomes in the metastatic setting. On the other hand, the genomic instability characteristic of MSI-H/dMMR tumors appears to be associated with decreased sensitivity to chemotherapy, and the benefits of standard adjuvant or neoadjuvant chemotherapy approaches in this subtype are being increasingly questioned. Here, we review the prognostic and predictive impact of MMR status in localized gastric and colorectal cancers, and highlight the emerging clinical data incorporating checkpoint inhibitors in the neoadjuvant setting.https://doi.org/10.1177/17588359231162577 |
| spellingShingle | Mélina Boutin Sharlene Gill Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting Therapeutic Advances in Medical Oncology |
| title | Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting |
| title_full | Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting |
| title_fullStr | Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting |
| title_full_unstemmed | Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting |
| title_short | Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting |
| title_sort | controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting |
| url | https://doi.org/10.1177/17588359231162577 |
| work_keys_str_mv | AT melinaboutin controversiesandmanagementofdeficientmismatchrepairgastrointestinalcancersintheneoadjuvantsetting AT sharlenegill controversiesandmanagementofdeficientmismatchrepairgastrointestinalcancersintheneoadjuvantsetting |