Triple-combination therapy patch shrinks tumors, prevents recurrence in colon cancer mice model

Investigators at Brigham and Women's Hospital have developed a hydrogel patch that can adhere to tumors in a preclinical model of colon cancer, delivering a local, combination treatment as the elastic gel breaks down over time. The new technique may allow clinicians to one day use diagnostic colonoscopy equipment to immediately deliver treatment without the need for open surgery at a later date. The team's findings are published in the July 25 issue of Nature Materials.

The researchers were able to deliver three therapeutic strategies in their mouse model of colon cancer: gene therapy, chemotherapy or thermal ablation or a combination of all three. The team used gold nanoparticles to deliver a gene therapy treatment that targets Kras, a known cancer gene, and used near-infrared radiation to release a chemotherapeutic and cause heat damage to the cancer cells. The local, triple-combination therapy not only shrank tumors but also had a sustained effect overtime, preventing tumor recurrence and significantly extending survival of mice.

The researchers examined the effects of the therapy both with and without resection (surgical removal of the tumor), which is the current standard treatment for colon cancer in humans. In human cases where resection is not possible, a neoadjuvant therapy, such as chemotherapy or radiation therapy, is often used to shrink tumors before clinicians attempt to remove them. Natalie Artzi, PhD senior author of the study and a principal investigator at BWH, and her colleagues anticipate that their hydrogel patch could someday be used to shrink tumors before resection or could eliminate the need for resection entirely. They plan to test the material in larger preclinical models and dive more deeply into the genetic changes resulting from therapy to pinpoint which genes are most critical to target.

"Our preclinical results are remarkable - by using local, combination treatment, we achieved complete tumor remission when the patch was applied to non-resected tumors and elimination of tumor recurrence when applied following tumor resection" said Artzi. "Next, we would like to use colonoscopy equipment to locally apply the patch to tumors in large preclinical models. Using minimally invasive techniques to apply the triple-therapy patch and evaluate its efficacy has the potential to improve clinical procedures and therapeutic outcomes."

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