In the study, a team from the Wellcome Sunner Institute in Cambridge, the European Bioinformatics Institute (EMBL-EBI) and Open Targets used Casper gene-editing technology to map the drug resistance landscape in certain types of cancer, including colon and lung cancer.
The researchers explained how known mutations affect drug resistance, and also highlighted new changes in DNA that warrant further exploration.
Drug resistance is one of the biggest challenges in cancer treatment, as mutations in cancer cells reduce the effectiveness of drugs over time. After resistance to initial treatment, subsequent treatments, known as second-line treatments, have limited options.
Therefore, understanding the molecular changes that cause this resistance is vital to uncover new therapeutic options.
To combine comprehensive information about cancer mutations, the researchers used the latest gene editing technology “Casper” and single-cell genomics techniques to study the effects of several drugs across human cancer cell lines and organoid cell models. By combining these techniques, they were able to create a map showing drug resistance mechanisms across different species, with a focus on colon and lung cancer and Ewing’s sarcoma.
The research team found that cancer mutations are divided into 4 categories according to their effect on DNA. These categories include: Drug resistance mutations: lead to reducing the effectiveness of medications, andDrug addiction mutations: It makes some cancer cells dependent on drugs for their growth, andDriver mutations: Gives cells the ability to use alternative signaling pathways for growth, andAllergenic variants: It makes cancer more sensitive to certain treatments, which means patients may benefit from specific medications.
The study focused on colon cancer, lung cancer, and Ewing’s sarcoma, as these types are resistant to treatment and lack effective second-line options.
The researchers used 10 medications that are either currently prescribed or in clinical trials, which helps shed light on new options.
Dr Matthew Coelho, senior author from the Wellcome Sanner Institute and Open Targets, said: “Developing cancer cells to resist treatments is a major challenge. “Our knowledge of mutations is a key way to understand how to deal with them, as mutations are divided into 4 groups that may require different treatment strategies.”
Dr. Magdalena Strauss, a participant in the study, added: “Using Casper gene editing technology and machine learning, we were able to analyze how mutations affect drug response. “This new framework will help researchers map common changes in DNA during treatment, which will help guide future clinical trials.”
The study was published in the journal Nature Genetics.
Source: Medical Express
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