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Scientists Find Possible Reason Why Immunotherapy Doesn’t Work For Some People

Immunotherapy is a godsend for cancer patients. However, not all patients respond positively to the therapy. A new study has a possible explanation as to why this occurs.

A recent study conducted by Yale School of Medicine researchers, published in the journal Cancer Discovery, found the fault may lie in the DNA repair in tumors.

“We wanted to understand why some patients respond better than others to immunotherapy,” co-corresponding author Ryan Chow, Yale’s Department of Genetics and the Systems Biology Institute, said, reported SciTechDaily.

According to the outlet, studies have found only half of the patients with highly mutated colorectal and endometrial cancers will respond to immunotherapy.

The Yale team based their findings on the analysis of a phase 2 study of 24 patients with endometrial cancer and the immunotherapy drug pembrolizumab.

The researchers pinned the reason why immunotherapy does not for some people on the failure of a process known as “mismatch repair.” 

Errors in the DNA are common during cell division. There is a special group of proteins that is responsible for DNA correction. These proteins identify and correct DNA errors through mismatch repair. 

Now, an impediment to this editing process occurs in many different types of cancer, leading to high mutation levels.

The researchers opined that the breakdown in the repairing process can occur in two different ways. First, mutations can occur in the DNA repair machinery itself, which can lead to the production of defective repair proteins. Second, the entire production of the DNA repair machinery can cease.

“An analogy would be a dysfunctional toy factory,” Chow said. “Maybe the factory makes broken toys that don’t work, or the factory has no personnel and stops producing toys altogether. Either way, kids won’t be happy.”

Still, the researchers found that tumors with defective DNA repair proteins responded significantly better to immunotherapy compared to those ones in which the production of DNA repair proteins had been halted.

The researchers said the differences between the two types of tumors can be attributed to the changes in the immune response that was in play against each of the tumors.

“When it comes to immunotherapy, it seems that the journey — in this case, the underlying cause of mismatch repair deficiency — may be just as important as the destination,” Chow commented.

“The innovative use of clinical trial data can guide our understanding of how immunotherapy manipulates the immune system and ultimately improve how we treat patients,” Dr. Eric Song, an ophthalmology resident at Yale, added.

Another study reported that sugary drinks may increase the risk of certain types of cancer.

“Results showed that consumption by men and women of greater than two SSB (Sugar-sweetened beverages) drinks a day versus people who never drank was not associated with all-cancer mortality, but was associated with increased risk of obesity-related cancers combined, which became null after adjustment for BMI,” the American Cancer Society noted in a news release.

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