dMMR - Cancer Science

What is dMMR?

Deficient Mismatch Repair (dMMR) refers to the loss of function in the mismatch repair (MMR) system, a critical mechanism that corrects errors during DNA replication. When the MMR system is compromised, it leads to the accumulation of mutations, which can contribute to the development and progression of cancer.

How is dMMR Detected?

dMMR can be detected through various diagnostic techniques, including immunohistochemistry (IHC) and microsatellite instability (MSI) testing. IHC involves staining tumor tissues to identify the presence or absence of MMR proteins, while MSI testing looks for changes in the length of microsatellite sequences, which are indicative of MMR deficiency.

Which Cancers are Associated with dMMR?

dMMR is most commonly associated with colorectal cancer and endometrial cancer, but it can also be found in other cancers such as gastric cancer, ovarian cancer, and prostate cancer. Understanding the presence of dMMR in these cancers can help tailor treatment strategies.

Why is dMMR Clinically Significant?

The presence of dMMR has significant clinical implications. Tumors with dMMR often exhibit a high mutation burden, making them more likely to respond to immunotherapy, particularly checkpoint inhibitors like pembrolizumab and nivolumab. These therapies can unleash the body's immune system to target and destroy cancer cells more effectively.

How Does dMMR Affect Treatment Decisions?

The detection of dMMR status in a tumor can influence treatment decisions. For instance, patients with dMMR colorectal cancer may benefit from immunotherapy rather than traditional chemotherapy. Similarly, dMMR status can guide the use of targeted therapies and participation in clinical trials designed to exploit the vulnerabilities of MMR-deficient tumors.

What are the Genetic Implications of dMMR?

dMMR can be caused by inherited genetic mutations, such as those found in Lynch syndrome, a hereditary condition that increases the risk of various cancers. Identifying dMMR can prompt genetic testing and counseling for patients and their families, allowing for proactive surveillance and management of cancer risk.

What Research is Being Done on dMMR?

Ongoing research is focused on understanding the molecular mechanisms underlying dMMR and developing new therapeutic strategies. Studies are also exploring the role of dMMR in predicting response to immunotherapy and other treatments. Advances in genomic sequencing and biomarker discovery are expected to further enhance our ability to diagnose and treat dMMR-associated cancers.

Relevant Publications

Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT): a clinicopathological analysis of four rare cases.

Issue Release: 2024

Immune checkpoint inhibitor combinations for patients with advanced endometrial cancer: a network meta-analysis and cost-utility analysis.

Issue Release: 2024

The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study.

Issue Release: 2024

Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Issue Release: 2024

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Issue Release: 2024

Cost-effectiveness of dostarlimab plus chemotherapy for primary advanced or recurrent endometrial cancer.

Issue Release: 2024

Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial.

Issue Release: 2024

Routine use of MSI testing in colorectal cancer using a proposed algorithm.

Issue Release: 2024

Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection.

Issue Release: 2024

Mismatch repair protein deficiency in triple-negative breast carcinomas.

Issue Release: 2024

Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis.

Issue Release: 2024

Mismatch repair deficiency: how reliable is the two-antibody approach? A national real-life study.

Issue Release: 2024

Deep learning to assess microsatellite instability directly from histopathological whole slide images in endometrial cancer.

Issue Release: 2024

Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

Issue Release: 2024

[Detection and Significance of Molecular Markers in Immunotherapy and Targeted Therapy of Colorectal Cancer in Tibet].

Issue Release: 2024

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated \"Big Bang\" pathway to CRC in three of the four Lynch syndromes.

Issue Release: 2024

Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial cancer.

Issue Release: 2024

PD-1 blockade plus COX inhibitors in dMMR metastatic colorectal cancer: Clinical, genomic, and immunologic analyses from the PCOX trial.

Issue Release: 2024

Death receptors 4/5 mediate tumour sensitivitNot applicably to natural killer cell-mediated cytotoxicity in mismatch repair deficient colorectal cancer.

Issue Release: 2024

Characterization of discordance between mismatch repair deficiency and microsatellite instability testing may prevent inappropriate treatment with immunotherapy.

Issue Release: 2024

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