July 20, 2024
CRISPR-Powered Technique Shows Promise for Treating Aggressive Brain Cancer

CRISPR-Powered Technique Shows Promise for Treating Aggressive Brain Cancer

Researchers from the Gladstone Institutes have discovered that the gene-editing technology known as CRISPR holds promise as a therapeutic strategy for primary glioblastoma, a highly aggressive and difficult-to-treat brain cancer. Their findings were published in the journal Cell Reports.

The team developed a novel technique called “cancer shredding,” in which they programmed CRISPR to target repeating DNA sequences that are specific to recurrent tumor cells. By snipping away at these cells, the researchers were able to destroy them while sparing healthy cells. The study used cell lines from a patient whose glioblastoma had returned after previous treatments.

Glioblastoma is the most common lethal brain cancer, and current treatment options are limited. Patients typically undergo chemotherapy, radiation, and surgery, but the majority experience relapse within months. The researchers aimed to find a new approach that could address the problem of recurrence.

Traditional cancer treatments often fail to eliminate all tumor cells. In the case of glioblastoma and other highly recurrent cancers, the surviving tumor cells develop genetic adaptations or mutations that enable them to proliferate. Building on their previous research, the Gladstone team hypothesized that these mutated cells have a unique genetic signature that can be targeted.

Using computational methods, they analyzed the entire genomes of cancer cells, focusing on non-coding DNA to identify shared repetitive code, even among cells with different mutations. Armed with this information, they were able to guide CRISPR to the mutated cancer cells and destroy them.

The researchers see CRISPR as a gateway to a new therapeutic approach that reduces the risk of tumor cell escape. This technique, known as cancer shredding, may have potential not only for glioblastoma but also for other hypermutated tumors.

Many of the experiments were conducted in Jennifer Doudna’s lab at Gladstone, where she serves as a senior investigator. Doudna was awarded the 2020 Nobel Prize in Chemistry for her co-discovery of the CRISPR-Cas9 gene-editing technology. Mitchel Berger, MD, a neurosurgeon and director of the Brain Tumor Center at UCSF, and Alexander Perez, MD, Ph.D., a resident at UCSF who contributed computational work, also played key roles in the study.

Until recently, CRISPR has mainly been used in therapy development and as a research tool, rather than as a treatment on its own. However, this changed in November when UK regulators approved the first CRISPR-based therapy for sickle cell disease and beta-thalassemia. The FDA is expected to issue a decision on the same therapy in the US in early December.

The Gladstone team acknowledges that there is still much work to be done before their findings can be translated into a therapy for patients. Challenges include determining the most effective delivery method for CRISPR in glioblastoma patients and minimizing unintended off-target effects.

Despite these challenges, first author I-Li Tan, Ph.D., who conducted the study as a postdoctoral researcher in Doudna’s lab, remains hopeful. Glioblastoma has long perplexed scientists, but with the precise targeting ability of CRISPR, Tan believes there is potential for a cure.

In addition to Fellmann, Doudna, Berger, Perez, and Tan, the study’s authors include Rachel Lew, Xiaoyu Sun, Alisha Baldwin, Yong Zhu, and Mihir Shah.

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1. Source: Coherent Market Insights, Public sources, Desk research
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