MENUAACR 2024: Ljungman speaks on “KLIPP,” a new technique targeting cancer with CRISPR
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In Swedish, klipp means both “to cut” and “opportunity.” Mats Ljungman, Ph.D., Rogel researcher and professor of radiation oncology, brings this framework to KLIPP, a new technique in precision medicine using CRISPR to target weak spots in cancer cells.
Ljungman shared his research at the 2024 American Association of Cancer Research Annual meeting in a session titled “Novel Approaches for Targeted Therapies.”
While chemotherapy and radiation are commonly used to treat tumors and destroy cancer cells, normal tissue will be harmed in the process leading to side effects for patients. CRISPR technology allows the possibility for oncologists to protect normal tissue, targeting DNA and inducing double strand breaks in tumor DNA similar to radiation but with more precise control. “If you find a unique vulnerability in a tumor, you can leverage that and induce breaks in the tumor only,” Ljungman explained.
KLIPP builds on CRISPR technology. An RNA therapy approach, KLIPP targets unique features in all cancer cells, or cancer-specific structural variant junctions, where the chromosomes have rearranged. Ljungman calls these points cancer’s “Achilles heel.” “We’ve known about these rearrangements for over 100 years, but we’ve never attacked or used them as a target until now,” he explained. “With CRISPR and whole genome sequencing, we can find where these rearrangements are and target them in each patient.”
KLIPP uses a split enzyme system to form and get activated specifically at junctions. “We’ve found that if we just target two or three of these junctions, it’s very toxic to cells,” Ljungman continued.
His team initially conducted this research with bladder cancer cells, but Ljungman says this could be applicable across tumor types. “The challenge is to deliver it,” he said.
This year at AACR, Ljungman hopes to generate interest in KLIPP and gain momentum in bringing this precision medicine technique to patients. “There’s often skepticism when we first share it with people, as there should be, because it’s a new concept. But when people understand what KLIPP can do, they are really supportive and understand our challenges,” Ljungman said.
“Eventually we want to bring this to clinical trial, but there’s not a lot of federal infrastructure to support personalized medicine. However, all tumors are genetically different and using personalized approaches, such as KLIPP, to target vulnerabilities unique for each tumor is the way of the future”