Researchers Develop a New Platform Technology For Personalized Cancer Treatment

Destroying cancer cells without affecting bordering normal cells is the most desirable method for targeted cancer treatment. However, it can not be easily accomplished because of the resemblances in the properties in between normal and cancer cells.

So scientists at the IBS developed an innovative strategy called CINDELA (Cancer-specific INDEL Attacker). Which invades cancer-specific mutations and causes multiple DNA double-strand breaks. To specifically cause cancer cell death. So It is hoped that CINDELA can end up being a possible approach for individualized cancer treatments in most tumors.

Meanwhile Diagnosis of cancer might be awful reports to patients and their family members. Conventional treatment alternatives such as radiation and chemotherapies usually kill not just cancer cells but also normal cells. Which results in painful effects.

Subsequently radiation and chemotherapies destroy cancer cells by producing DNA double-strand breaks in their DNA. Since both treatments aim for DNA in both normal and cancer cells. Radiation and chemo-drugs can not differentiate between cancer and normal cells. Thus, unplanned destroying of healthy cells and adverse effects are inevitable when using these procedures. Researchers have extensive sought a method to selectively target only cancer cells without having an effect on normal cells. Which is a crucial criteria for ideal cancer treatment.

New cancer treatment routes

There have been two major advancements in the biomedical science fields lately. One is cancer genomics, and the other is the finding of a site-specific endonuclease, called CRISPR-Cas9 (typically called genetic scissors). Cancer genomics projects have found that regardless of their origins, most cancer cells build up many mutations. Including small insertion/deletion (InDel) of several nucleotides, single nucleotide changes, and large chromosomal aberrations. CRISPR-Cas9, the discovered by the 2020 Nobel Prize in chemistry. Is a technology that can be used to make DNA double-strand breaks in a sequence-specific manner.

South Korean researchers in the Center for Genomic Integrity (CGI) within the Institute for Basic Science (IBS). Integrated these two ideas and suggested a new idea for cancer treatment. By using CRISPR-Cas9 to produce DNA double-strand ruptures at cancer-specific mutations that only remain in cancer cells. They suggested a possibility of triggering cell death in cancer cells without affecting normal cells.

Three CGI research study groups (laboratories led by MYUNG Kyungjae, KWON Taejon, and CHO Seung Woo). Located in the Ulsan National Institute of Science and Technology (UNIST). Collaborated and demonstrated that it is indeed possible.

First, the specialists verified that enzyme-driven DNA double-strand breaks using CRISPR. Were able to cause cell deaths in cancer similar to physical or chemical breaks driven by radiation or chemotherapies, respectively. They did bioinformatics analysis to identify unique InDel mutations in several various cancer cell lines. Including breast, colon, leukemia and glioblastoma. Which are not discovered in normal cells. Based on this information, they successfully made CRISPR-Cas9 reagents targeting those mutations.

CINDELA

The scientists named this new treatment CINDELA. Which stands for “Cancer-specific InDel Attacker.” CINDELA was found to precisely destroy cancer cells without affecting normal cells. It was found that CINDELA-driven cancer cell death was dependent on the number of DNA double-strand breaks developed by CRISPR-Cas9. CINDELA reagent, which caused 50 breaks in the DNA. Was better at destroying cancer cells than the reagent that caused only 10 breaks.

So along with cancer cell line experiments. Scientists conducted additionally animal studies to verify CINDELA’s efficiency in living organisms. To perform so, tumor cells (colon and lung cancer) were originated from patients and were xenografted into mice. It was found that the CINDELA treatment can substantially suppress the growth of tumors in these mice.

Notably, since CINDELA targets InDel mutations. Which are generated as byproducts during tumorigenesis, CINDELA can be used on treat most tumors. “We believe CINDELA can become a novel therapeutic application for cancer treatments. As individualized and precision medicine for all cancer patients without severe side effects,” . The CGI Director Myung explained.

Future actions

As a next milestone, researchers have started utilizing this innovation in tumors directly taken from patients. With research groups having expertise in the relevant technologies. As gene delivery, companion diagnostic platform, and cancer genomics.

However, one obstacle that the researchers confronted in the course of these experiments was the delivery of CINDELA reagents to tumors. They achieved significant tumor growth inhibition using a high titer of the virus to deliver the CRISPR in mice. As of yet, this may not be enough to directly treat human patients. Such an obstacle is one of the major concerns in the current CRISPR-Cas9 field. Researchers believe that in the near future, the advancement of new delivery systems will eventually help establish the CINDELA cancer treatment innovation in cancer patients.

Read the original article on Medical Xpress.

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