The tissue surrounding a tumor acts differently compared to distant areas. The cancer cells from the tumor manipulate their environment, hindering the body’s immune system and creating a protective niche that allows tumor growth. While some treatments aiming at these pro-tumor effects have shown effectiveness in various cancers for certain patients, they often have little impact on others. Recently, researchers have come up with a fresh strategy that targets multiple pro-tumor actions simultaneously, demonstrating its ability to reduce tumor growth across several cancer types. This new approach could potentially provide a treatment option that benefits more patients than the current therapies available.
The tissue surrounding a tumor acts differently compared to distant areas. The cancer cells from the tumor manipulate their environment, hindering the body’s immune system and creating a protective niche that allows tumor growth. While some treatments aiming at these pro-tumor effects have shown effectiveness in various cancers for certain patients, they often have little impact on others.
Researchers at Yale have introduced a novel method that concurrently addresses several of these pro-tumor mechanisms, proving effective in decreasing tumor growth in multiple cancer types.
Their significant findings, published on January 16 in Nature Biotechnology, suggest a promising new treatment that could benefit a wider range of patients compared to existing therapies.
“Conventional therapies tend to focus on a single molecule within the tumor environment, but given its complexity, this approach can be insufficient,” stated Sidi Chen, an associate professor of genetics and neurosurgery at Yale School of Medicine and the lead author of the study. “For instance, renowned immunotherapy methods only show benefits for about 20 to 30% of patients.”
When these treatments fail, it may be due to the targeted molecule not significantly influencing the individual’s tumor, or an alternative molecule compensating for the one being targeted.
“The situation could also involve intricate networks of pathways within the tumor environment that work collectively to dampen the body’s immune response,” explained Chen, who is affiliated with the Systems Biology Institute at Yale’s West Campus. “So the challenge is how to simultaneously target multiple elements?”
For their innovative strategy, Chen and his team utilized a gene-editing tool called Cas13 that specifically targets and breaks down RNA, in contrast to its more commonly known relative, Cas9, which focuses on DNA. A key advantage of Cas13 is its capacity to aim at several genes with a single molecular delivery. The researchers identified various genes that suppress immune responses and designed a Cas13 system targeting each one of them.
Upon introducing the Cas13 component into mouse tumor environments, they observed that it silenced immune suppression genes (effectively reviving the immune system), remodeled the surroundings, and enhanced immune responses against tumors. This led to reduced tumor growth in four cancer types: breast cancer, melanoma, pancreatic cancer, and colon cancer.
Although further studies will be needed to fine-tune this approach for both effectiveness and safety, researchers believe this technology shows promise as an “off-the-shelf” treatment for broader applications and can also be customized for individual patients by adjusting gene targets as needed.
The team plans to advance this research path with the aim of moving toward translation and clinical trials.
Coauthors Feifei Zhang, Guangchuan Wang, and Ryan Chow, all from Yale, collaborated with Chen on this research.
