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Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer
Wen-Xuan Fan1,2, Fei Su1,2, Yan Zhang2,3
1Graduate School of Shanxi Medical University, Taiyuan, Shanxi, 030607, China.
Abstract:
Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It's recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.
Insights
This review explores mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC). It highlights the need for tailored treatments for subtypes like Lynch syndrome, as current therapies lack subgroup differentiation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a leading global malignancy.
- Molecular subtypes, specifically mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), are crucial for treatment selection.
- Understanding subtypes like Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic dMMR/MSI-H CRC is essential.
Purpose of the Study:
- To review current molecular classifications of dMMR/MSI-H CRC and its subtypes.
- To analyze the implications of these molecular characteristics on treatment and prognosis.
- To identify limitations in current clinical trials and emphasize the need for subtype-specific therapeutic strategies.
Main Methods:
- Comprehensive literature review of molecular classifications.
- Analysis of clinical trial data regarding immune checkpoint inhibitors in dMMR/MSI-H CRC subgroups.
- Synthesis of information on completed and ongoing clinical studies.
Main Results:
- dMMR/MSI-H status significantly impacts CRC treatment and prognosis.
- Current clinical trials have not definitively distinguished immune checkpoint inhibitor efficacy across LS, LLS, and sporadic subtypes.
- There is a critical need for more refined clinical studies to guide tailored therapies.
Conclusions:
- Molecular profiling is key for understanding and treating dMMR/MSI-H CRC.
- Further research is required to develop personalized treatment strategies for distinct CRC molecular subtypes.
- Aligning therapeutic development with specific molecular profiles will improve patient outcomes.
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