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New precision drugs based on the exact genetic mutations that drive the cancer are needed to help patients diagnosed with some form of cancer each year.
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Comprehensive Analysis Reveals 370 Novel Anticancer Drug Targets

Second generation of the Cancer Dependency Map uncovers priority drug targets with strong links to specific cancer types

Wellcome Trust Sanger Institute
Published:Jan 12, 2024
|3 min read
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A new, systematic analysis of cancer cells identified 370 candidate priority drug targets across 27 cancer types, including breast, lung, and ovarian cancers. By looking at multiple layers of functional and genomic information, researchers were able to create an unbiased, panoramic view of what enables cancer cells to grow and survive. They identified new opportunities for cancer therapies in a significant leap towards a new generation of smarter, more effective cancer treatments.

In the most comprehensive study of its kind, researchers from the Wellcome Sanger Institute, Open Targets, and their collaborators, pooled together data from 930 cancer cell lines. They then used machine learning methods to find the drug targets that show the most promise for developing new treatments, and the patients who would most benefit from such treatments. This involved assessing the occurrence of these targets in actual patient tumors and linking them to specific biological markers and genetic and molecular features found in the tumors.

The findings, published recently in Cancer Cell, not only bring researchers one step closer to producing a full Cancer Dependency Map—whose first iteration was published in 2019—of every vulnerability in every type of cancer, but also guide focused efforts to accelerate the development of targeted cancer treatments.

Lack of specificity in traditional cancer treatments

Many types of cancer currently lack effective treatments, such as liver and ovarian cancers. Chemotherapy and radiotherapy are effective treatments, but cannot distinguish normal cells from cancerous ones, and hence, cause damage throughout the entire body with harsh side effects, such as extreme fatigue, nausea, and hair loss. New precision drugs based on the exact genetic mutations that drive the 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 costly and inefficient.

With over 20,000 potential anticancer targets in the genome, determining which are suitable to target for specific types of cancers and patients is a significant challenge.

In this new study, researchers from the Wellcome Sanger Institute and their collaborators set out to narrow down potential drug targets. By analyzing data available from the Cancer Dependency Map project, which involved CRISPR technology to disrupt every gene inside 930 human cancer lines one at a time, they were able to produce the most comprehensive view of potential new cancer targets to date.

Charting cancer dependencies

The researchers first identified weaknesses within different cancer types: Genetic dependencies that could be harnessed to make new therapies. They then linked those weaknesses to clinical markers to identify patients in which those therapies would be most effective. Finally, they explored how dependency marker-pairs fit into known networks of molecular interactions within cells, providing clues as to how cell biology is disrupted by cancer, and which targets might yield the most effective therapies.

The work provides a clearer understanding of which types of cancer can possibly be treated by existing drug discovery strategies and pinpoint areas where novel and innovative approaches are needed.

The findings underscore the importance of tailoring treatments to the unique characteristics of each cancer, promising more personalized care for patients with fewer side effects in the future.

Marianne Baker, PhD, science engagement manager at Cancer Research UK, said, “Two people might have the same type of cancer, but their diseases can behave differently. That is why we need precision medicine. This ambitious work is a compelling example of research informing drug discovery from the start, paving the way for more effective precision cancer therapies. Giving people treatments for their unique cancer can improve the odds of success and help more people affected by cancer live longer, better lives.”

- This press release was originally published on the Wellcome Sanger Institute website