[MSI Metastatic solid tumors treatment and immunotherapies]

Area of Science:

• Oncology
• Immunotherapy
• Molecular Diagnostics

Background:

• Microsatellite instability (MSI) phenotype is observed in various cancers, with high incidence in uterine and gastric tumors.
• MSI tumors, characterized by DNA mismatch repair deficiency (dMMR), exhibit increased mutational load and neo-antigen production.
• Checkpoint inhibitors have demonstrated significant efficacy in MSI colorectal cancers, prompting investigation in other tumor types.

Purpose of the Study:

• To review clinical outcomes of checkpoint inhibitors in non-colorectal cancers with MSI phenotype.
• To explore the association between MSI and other tumor characteristics.
• To highlight ongoing clinical trials for immunotherapy in this patient population.

Main Methods:

• Literature review of clinical outcomes and ongoing trials.
• Analysis of MSI incidence rates in various non-colorectal cancer types.
• Discussion of the biological underpinnings of MSI and immunotherapy response.

Main Results:

• Checkpoint inhibitors achieve response rates over 50% in pre-treated advanced endometrial and metastatic gastric cancers, often in combination with chemotherapy.
• MSI phenotype incidence varies significantly across non-colorectal cancers, notably high in endometrioid uterine cancers and gastric tumors.
• The prognostic value and clinical associations of MSI in non-colorectal cancers require further investigation.

Conclusions:

• Checkpoint inhibitors represent a promising therapeutic strategy for non-colorectal cancers exhibiting MSI.
• Reliable predictive biomarkers for immunotherapy response in MSI tumors are crucial for clinical application.
• Further research and clinical trials are warranted to optimize checkpoint inhibitor therapy in diverse MSI-positive cancers.