New approach shows promise in fighting multiple types of cancer

New approach shows promise in fighting multiple types of cancer

The tissue next to a tumor behaves differently than areas further away: the tumor's cancer cells influence their environment, blocking the body's immune defenses and creating a kind of harbor in which the tumor can grow. Treatments that target some of these pro-tumor actions are effective in a range of cancers, but only in some patients. In other cases, these treatments have little effect.

Yale researchers have developed a new approach that simultaneously targets some of these pro-tumor effects, which have shown they can effectively reduce tumor growth across different cancer types.

Their new findings, published January 16 innatural biotechnology,Point to a potential new treatment that will benefit more patients than current therapeutic options.

Traditional therapies target a molecule in the tumor microenvironment, but the microenvironment is so complex that targeting one thing doesn't always work. For example, the most popular of these immunotherapies only benefits 20 to 30% of patients. “

Sidi Chen, senior author and associate professor at Yale School of Medicine

When these therapies don't work, it may be because the molecule they target is damaged by the treatment.

"Or it may be even more complex, if a large network of pathways within the tumor microenvironment all work to suppress the body's immune response," said Chen, who is also a researcher in the Systems Biology Institute on Yale's West Campus. “So, how do you achieve multiple goals in the same case?”

For their approach, Chen and his colleagues used a gene-editing molecule called Cas13, which targets and degrades RNA. (Its widely used counterpart, known as Cas9, targets DNA.) One advantage of Cas13 is the ability to target multiple genes with one molecular package. Therefore, the researchers identified several genes that suppress immune responses and developed a Cas13 system that targeted each of them.

When they engineered the Cas13 package into mice in tumor microenvironments, they found that it silenced these immunosuppressive genes (essentially venting or reactivating the immune system), remodeled the microenvironment, and increased antitumor immune responses. The result was reduced tumor growth in four types of cancer: breast cancer, melanoma, pancreatic cancer and colon cancer.

While further research will be required to further optimize this approach for effectiveness and safety as needed.

The researchers are continuing this line of research, with the aim of working towards translational and clinical studies.

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