A new, systematic analysis of cancer cells has identified 370 potential drug targets in 27 cancer types, including breast, lung, and ovarian cancer.
By examining multiple layers of functional and genomic information, researchers gained an unbiased, comprehensive understanding of what enables cancer cells‘ growth and survival. They identified new opportunities for cancer therapies, making significant progress towards a new generation of more intelligent and effective cancer treatments.
In the most comprehensive study of its kind, researchers from the Wellcome Sanger Institute, Open Targets, and their colleagues combined data from 930 cancer cell lines. They then used machine learning methods to find the drug targets most promising for developing new treatments and the patients who would benefit the most from such treatments. This involved assessing the occurrence of these targets in actual patient tumors and linking them with specific biological markers, genetic and molecular characteristics found in the tumors.
The results published today (January 11th) in Cancer Cell bring researchers one step closer to creating a comprehensive cancer dependency map. We are helping to identify every vulnerability in every cancer type and make targeted efforts to accelerate the development of tailored cancer treatments.
There are many cancer types for which there are currently no effective treatments, such as liver and ovarian cancer. Chemotherapy and radiation therapy are effective treatments, but cannot distinguish between normal and cancerous cells, causing damage throughout the body with serious side effects such as extreme fatigue, nausea, and hair loss.
New precision drugs based on the genetic mutations that cause cancer are needed to help the millions of patients diagnosed with some form of cancer each year, responsible for one in six deaths worldwide. However, drug development has a 90 percent failure rate, making it both expensive and inefficient.
With over 20,000 potential cancer targets in the genome, it is a significant challenge to determine which are suitable as a target for specific cancer types and patients.
In this new study, researchers from the Wellcome Sanger Institute and their colleagues sought to narrow down potential drug targets. By analyzing the data available from the Cancer Dependency Map project, where CRISPR technology was used to individually destroy each gene in 930 human cancer cell lines, they were able to create the most comprehensive overview of potential new cancer targets to date.
The work provides a clearer understanding of which cancer types may be treated with existing drug development strategies and highlights areas where new and innovative approaches are needed.
The results underscore the importance of tailoring treatments to the unique features of each cancer type, promising a more individualized approach to patient care with fewer side effects in the future.
Dr. Francesco Iorio, co-lead author of the study from the Computational Biology Research Center of Human Technopole, said: „By analyzing the most extensive data set on cancer dependency to date, we present the most comprehensive map of human cancer vulnerabilities, identifying a new list of targets with the highest priority for potential treatments and providing evidence of which patients could benefit most—all made possible through the development and application of innovative methods of computer and machine intelligence.“
Dr. Mathew Garnett, co-lead author of the study at the Wellcome Sanger Institute and Open Targets, said: „Our work uncovers 370 potential top-priority targets for combating the most common cancer types, including breast, lung, and colorectal cancer. This work leverages the latest insights from genomics and computational biology to understand how we can best combat cancer cells. This will help drug developers concentrate their efforts on targets with the highest value and bring new drugs to patients more quickly.“
„Two individuals may have the same type of cancer, but their diseases can behave differently. That’s why we need precision medicine. This ambitious work is a compelling example of research influencing drug development from the start and paving the way for more effective precision cancer therapies. When people receive treatments for their individual cancer, the prospects of success improve and more people affected by cancer are helped to live longer and better lives.“
Dr. Marianne Baker, Science Engagement Manager, Cancer Research UK
Wellcome Sanger Institute
Pacini, C., et al. (2024). A comprehensive clinically-based map of dependencies in cancer cells and a framework for target prioritisation. Cancer Cell. doi.org/10.1016/j.ccell.2023.12.016.