Researchers from Baylor College of Medicine, along with their partners, have identified promising new targets for cancer therapy and gained new insights into existing cancer drugs. By integrating data from proteomics, genomics, and epigenomics across 10 types of cancer, the team pinpointed protein and peptide targets in cancer tissues. Many of these targets were validated experimentally as viable candidates for new therapeutic strategies. The findings were published in the journal Cell.
“Targeted therapies, which are cancer treatments aimed at specific proteins in cancer cells, have shown to be more effective than traditional radiotherapy and chemotherapy,” said Dr. Bing Zhang, co-corresponding author, professor of molecular and human genetics, and member of the Lester and Sue Smith Breast Center at Baylor. “Despite advancements in identifying cancer vulnerabilities, fewer than 200 proteins are targeted by FDA-approved cancer drugs. Our study has significantly expanded the list of potential therapeutic targets by analyzing data from over 1,000 tissue samples across 10 cancer types.”
The researchers used computational tools to integrate proteogenomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), which includes DNA, RNA, and protein information from treatment-naïve primary tumors, many of which had matched normal tissues for comparison. By merging this dataset with other public data, they explored the gene and protein alterations in various tumors, identifying protein targets for cancer therapy.
“Our aim was to better understand known drug targets and discover new ones that could lead to drug developments,” said Zhang, a McNair scholar and member of Baylor’s Dan L Duncan Comprehensive Cancer Center.
The team’s data integration approach systematically identified proteins and genes critical for cancer growth. This included proteins overexpressed or hyperactive in cancer tissues and the loss of tumor suppressor genes, which can create dependencies on other proteins that could be targeted therapeutically. They also looked for tumor antigens, including neoantigens—cancer-specific peptides from gene mutations.
“Our study found new opportunities to repurpose existing drugs. For instance, we demonstrated that an antifungal drug could reduce the growth of several cancer types, indicating its potential as an anti-cancer treatment.”
Dr. Bing Zhang, Professor of Molecular and Human Genetics, Baylor College of Medicine
Additionally, the researchers found potential protein targets without current drugs, such as kinases and cell surface proteins. “These discoveries open doors for drug development, including small-molecule drugs or drug-antibody conjugates,” Zhang said.
The computational identification of several tumor-associated proteins across different cancer types was followed by experimental validation in lab-grown cells and animal models, confirming their potential as therapeutic targets.
“I am thrilled that we have created a comprehensive resource of protein targets, greatly expanding the therapeutic landscape by identifying numerous new candidates and covering various therapeutic modalities. We have made our findings publicly available at https://targets.linkedomics.org,” Zhang stated. “We hope this resource will facilitate the repurposing of existing drugs and the development of new cancer therapies.”
