Immunotherapy and metastatic colorectal cancers with microsatellite instability or mismatch repair deficiency

Area of Science:

• Molecular Oncology
• Gastrointestinal Cancer Research
• Immunotherapy Biomarkers

Background:

• Microsatellite instability (MSI) indicates defective DNA mismatch repair (dMMR), present in ~5% of metastatic colorectal cancers (mCRC).
• MSI is a key predictive biomarker for immune checkpoint inhibitor (ICKi) efficacy in mCRC patients.
• Conventional chemotherapy often shows limited efficacy in chemoresistant MSI/dMMR mCRC.

Purpose of the Study:

• To review the efficacy of conventional cytotoxic regimens in MSI/dMMR mCRC.
• To highlight clinical activity of ICKi in chemoresistant MSI/dMMR mCRC.
• To discuss ongoing clinical trials and challenges in treating MSI/dMMR mCRC.

Main Methods:

• Literature review of studies on cytotoxic regimens and ICKi in mCRC.
• Focus on clinical activity data for ICKi in MSI/dMMR mCRC.
• Analysis of current clinical trials and emerging treatment challenges.

Main Results:

• Summary of literature on conventional cytotoxic regimens for mCRC.
• Evidence demonstrating significant clinical activity of ICKi in chemoresistant MSI/dMMR mCRC.
• Identification of ongoing trials and key challenges in this patient population.

Conclusions:

• MSI/dMMR status is crucial for predicting ICKi response in mCRC.
• ICKi represent a promising therapeutic option for chemoresistant MSI/dMMR mCRC.
• Further research and clinical trials are needed to address treatment challenges.