Turning Cancer Cell Mutations Against Themselves: A 'Fourth-Generation Anticancer Drug' Challenge [Reading Science]

Kyungjae Myung's IBS Research Team Develops 'CINDELA'
Efficacy Demonstrated in More Than 10 Cancer Types

A new anti-cancer therapy is being developed that uses mutations found in cancer cells as "targets" to kill those very cells. This treatment analyzes a patient's cancer genome to identify genetic sequences unique to cancer cells and then attacks them using gene-editing tools. The research team ultimately envisions advancing the technology into a personalized medicine system that creates a “one-patient-one-anticancer drug” tailored to the unique mutations in each patient’s cancer.

Myungkyung Jae, Head of IBS Genome Homeostasis Research Group, is explaining the 'CINDELA (Cancer-specific InDel Attacker)' technology. Photo by Kim Joungho

According to the Institute for Basic Science (IBS) on August 10, the research team led by Kyungjae Myung, head of the Genome Homeostasis Research Center, has developed a technology called CINDELA (Cancer-specific InDel Attacker), which selectively eliminates cancer cells by targeting their unique genome variations. The team is conducting follow-up studies. The researchers have positioned CINDELA as a candidate for a "fourth-generation anti-cancer drug," differentiating it from traditional treatments. The mechanism of CINDELA uses CRISPR-Cas9 to recognize and cut new genetic sequences created by mutations in cancer cells, resulting in cell death.

The core of CINDELA lies in exploiting the mutations produced by cancer cells. Cancer arises from an accumulation of mutations in the DNA sequence, resulting in many differences from normal cells. The research team designed gene-editing tools to identify and target the insertions and deletions (InDel mutations) that are present in cancer cells but absent in normal cells.

When the gene-editing tool recognizes the target sequence, it cleaves the cancer cell's DNA. Because these target mutations do not exist in normal cells, the attack can specifically target only cancer cells, according to the research team. In practice, the team confirmed that when targeting cancer cell-specific InDel mutations, only the cancer cells were selectively eliminated.

Existing treatments, such as radiation therapy and chemotherapy, kill rapidly dividing cancer cells but can also affect normal cells, which leads to side effects like hair loss, diarrhea, and reduced immune function. CINDELA aims to overcome these limitations by directly targeting the genomic differences between cancer and healthy cells.

Designing Treatments Based on Patient Mutations, Not Cancer Types

Another key feature of CINDELA is that, unlike conventional targeted therapies which focus on a specific cancer type or a single gene, it attacks newly formed genome sequences found only in cancer cells. The team confirmed CINDELA's cancer cell-selective killing effect on cell lines derived from leukemia, colorectal cancer, liver cancer, breast cancer, ovarian cancer, cervical cancer, and more. So far, effectiveness has been verified in over 10 cancer types.

The research team led by Kyungjae Myung, Head of the Institute for Basic Science (IBS) Genome Homeostasis Research Group, has developed a technology called 'CINDELA (Cancer-specific InDel Attacker)' that selectively attacks cancer cells by targeting their unique genome variations, and is conducting follow-up studies. Provided by Kyungjae Myung

The potential of CINDELA has also been confirmed in animal studies. The research team validated its effect in mouse models of cancer. These findings were published last year in the international journal "Cancer Research." The team has also reported results showing a reduction in liver tumors transplanted into the liver after CINDELA administration, as presented in their materials. However, this particular result has not yet been published as a paper.

The team is also exploring the possibility of combination therapy with existing anticancer drugs. When CINDELA, which is designed to cut single strands of DNA, was used with PARP inhibitors such as Olaparib, a synergistic effect was observed. The researchers are conducting further studies to see if this could reduce the number of genetic targets required to kill cancer cells.

Ultimately, the team's vision is to establish a personalized cancer therapy platform. This involves analyzing a patient's whole genome sequence (WGS) to identify InDel mutations that do not appear in healthy cells, then designing a CRISPR-Cas9 agent to target them. Next, using delivery vehicles such as viruses or nanoparticles, the therapy is tested at the cellular level before being administered to patients. The process, as outlined in their materials, consists of whole genome analysis and CRISPR design → CRISPR-Cas9 creation → virus/nanoparticle delivery → cell validation → patient treatment.

The Goal: Design Personalized Anticancer Drugs within a Month ... The Challenge: Delivery to Cancer Cells

In a press briefing, Myung forecasted that if this process is automated, it would take about a month to produce a tailored drug candidate after obtaining a patient's genome information. He explained that genome analysis would take about a week, and additional time would be needed for target selection and the design and synthesis of the required RNA for treatment.

However, significant hurdles remain before this becomes a practical treatment for patients. One major challenge is developing technology to efficiently deliver CINDELA to cancer cells. The team is currently comparing delivery efficiencies using lipid nanoparticles (LNPs) from various companies. They expect that combining these with targeting technologies that selectively find cancer tissues could enhance therapeutic effects even further.

Myung Kyungjae, Director of the IBS Genome Homeostasis Research Center, is explaining the 'CINDELA (Cancer-specific InDel Attacker)' technology. Provided by IBS

Another challenge is verifying the safety of a personalized drug designed anew for each patient. Although the core CRISPR-Cas9 protein remains the same, the guide RNA sequence changes to match each individual’s mutation. Myung noted that whether a new safety evaluation is required each time the guide RNA changes will become a significant regulatory issue as the field of personalized gene therapies develops.

To address this, the research team is also working to identify common mutations shared by multiple cancer patients. By pre-developing CINDELA agents that target these common mutations and verifying their safety in advance, the burden of developing custom drugs from scratch for each patient could be reduced.

So far, CINDELA has not yet reached clinical trials in humans. Its potential has been demonstrated in cell and animal studies, and follow-up development is ongoing after the technology was transferred to industry partners. Further preclinical research is needed before the treatment can be applied clinically.

Myung said, "If we can utilize the mutations present in a patient's cancer cells, we can design therapeutics based on personalized targets." He added, "Ultimately, our goal is to build a platform that enables us to rapidly create and deliver treatments matched to the cancer genome of each individual patient."

This content was produced with the assistance of AI translation services.