Researchers at Baylor College of Medicine (US) and collaborating institutions have discovered new potential therapeutic targets for cancer and new insights into the targets of existing cancer drugs, expanding the possibilities for treating this disease.
Using a comprehensive approach that included integrating proteomic, genomic, and epigenomic data from 10 cancer types, the team identified proteins and small protein or peptide targets in cancer tissue, and experimentally validated several of them as promising candidates for therapeutic strategies. The study appears in Cell.
“The trial has shown that targeted therapies, cancer treatments that target specific proteins in cancer cells, show promise in achieving more effective clinical outcomes than conventional radiotherapy and chemotherapy,” comments co-author Dr. Ping Zhang, professor of molecular and molecular sciences. Human Genetics and part of the Lester and Sue Smith Breast Center at Baylor.
“Although progress has been made in identifying potential vulnerabilities for certain types of cancer, FDA-approved cancer drugs target fewer than 200 proteins. In this study, we have significantly expanded the list of potential therapeutic targets by analyzing data from more From 1000 tissue samples covering 10 cancer types.
The researchers applied computational tools to integrate proteomic data comprising genome-wide information on DNA, RNA, and proteins generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) from prospectively collected primary tumor samples without prior treatment, many of which Contains compatible normal adjacent tissue.
The team combined the CPTAC dataset with other public datasets to investigate similarities and differences between genetic and protein alterations found in different tumor types to shed light on protein targets for cancer treatment.
“Our goal was to better understand the properties of known drug targets,” says Zhang, a McNair researcher and member of the Dan L. Duncan Comprehensive Cancer Center at Baylor. “We also hoped to identify new targets that could lead to the development of new drugs.”
The team applied a data integration approach to systematically identify proteins and genes important for cancer growth and progression.
For example, proteins that are overexpressed or hyperactive in cancerous tissues but not in their normal counterparts, and loss of tumor suppressor genes, which can create dependencies on other proteins that can then be targeted therapeutically.
They also looked for tumor antigens, including neoantigens, which are cancer-specific peptides derived from genetic mutations in tumors.
“Our study has revealed new opportunities to repurpose drugs currently approved for other conditions,” says Zhang. “For example, we show that an antifungal drug can also reduce the growth of several types of cancer, supporting further exploration of the anticancer value of this drug.”
The researchers also identified potential protein targets that currently lack a drug: some are enzymes called kinases and others are cell surface proteins. “These findings open opportunities for drug development, including small-molecule drugs or antibody-drug conjugates,” Zhang says.
Furthermore, the computational identification of several tumor-associated proteins common to different types of cancer was followed by experimental confirmation of their importance for cancer in cells grown in vitro and in animal models, validating these proteins as potential therapeutic targets worthy of further study.
“I am very excited to create a comprehensive resource of protein targets, significantly expanding the therapeutic landscape by identifying many new candidates and covering multiple therapeutic modalities,” concludes Zhang.
“We hope that this resource will pave the way for the reuse of currently available drugs and the development of new therapies to treat cancer.”
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