Tag Archives: MSI

DNA Mismatch Repair and 5-FU: What's the Connection?

Some colon cancer patients don’t benefit from treatment with 5-FU based chemotherapy and may even have worse outcomes than if they no chemo at all. Of every 100 people with colon cancer, about 15 will have cancers that arise when mistakes in DNA during cell division are not caught and fixed.  Scientists call this defective mismatch repair or dMMR. More often, colon cancer occurs when mutations in chromosomes accumulate but DNA repair pathways remain intact and mismatch repair is proficient (pMMR). This is true for about 85 percent of colon cancer. Both prognosis and the potential benefit from FU-based chemotherapy appear to be very different for these two types of

Some Colorectal Cancers Not Connected to Obesity

Although being obese increases risk for most colon and rectal cancers, the connection isn’t true in all types of colorectal cancer. Cancers that are linked to microsatellite instability (MSI) don’t appear to be influenced by obesity, strengthening the belief that MSI cancers come about differently than the average colorectal cancer. Overall, in a recent study, body mass index and weight gain during adult life increased risk of colorectal cancer by about 30 percent for men and 20 percent for women. However, increased risk was limited to microsatellite stable or microsatellite low tumors.

FOLFOX Effectiveness Not Related to DNA Mismatch Repair or MSI

Colon cancers that are caused by defects in genes that repair damaged DNA don’t respond well to 5-FU treatment after surgery. However, a new analysis of patients treated with FOLFOX (oxaliplatin, leucovorin, and 5-FU) found no differences between patients with deficient mismatch repair tumors and those with normal gene expression. In this small study of 135 patients, the research team concluded that adding oxaliplatin to 5-FU and leucovorin may overcome resistance to chemotherapy in mismatch repair deficient and microsatellite instable (MSI) colon cancer.

Stage III MSI High Colon Cancer May Benefit from Irinotecan

About 15 percent of people with stage III colon cancer may have fewer recurrences and better survival when they are treated with irinotecan. Although all stage III colon cancers don’t have an additional benefit when irinotecan is added to bolus 5-FU and leucovorin in a treatment called IFL, this smaller group does. About 15 percent of colon cancers develop when damaged DNA is not repaired and mutated cells grow into malignant tumors.  So-called deficient mismatch repair (dMMR) tumors have features different from most colorectal cancer, including a better prognosis.  They also have a very poor response to 5-FU-based chemotherapy. However, researchers studying tumor tissue from patients enrolled in a clinical trial

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