A new study from Baylor College of Medicine targets specific proteins that cause tumor growth as a potential personalized treatment for breast cancer.
The collaboration by researchers at Baylor College of Medicine, Washington University School of Medicine and the Broad Institute of MIT and Harvard have developed a new method to treat breast cancer by targeting the specific proteins that are responsible for tumor growth and test drugs that can neutralize the biological drivers.
“Here we study the problem of how to design more effective cancer treatments with a two-pronged approach,” Dr. Matthew Ellis, professor and director of the Lester and Sue Smith Breast Cancer Center at Baylor, said in a press release. “We combine patient-derived xenografts and proteogenomic integration.”
Patient-derived xenografts are a sample of a human cancer tumor that is transplanted into a lab mouse.
“We grow human tumors direct from patients in laboratory mice because we want to mimic the living natural environment tumor cells grow in — a beating heart, blood vessels and other biological structures — that is a natural as we can possibly make it,” Ellis said. “We think this approach offers a closer representation of the tumor’s growth environment to study cancer drugs than cells growing on a laboratory plastic dish.”
Previous research exhibited how this method can work as patient-derived xenografts of breast cancer tumors recapitulate most of the genes expressed and the proteins found in the original breast tumors. The xenografts also appear to respond to drug treatments similarly as tumors in human patients.
Cancer cells differ from normal cells in the types of genes expressed and also in some of the proteins used to carry out their functions.
“Proteins carry out most of the biological functions in the cell,” said Dr. Li Ding, associate professor of medicine at Washington University School of Medicine. “Knowing the DNA sequence of genes does not automatically tell us everything about the proteins doing work in the cells.”
Researchers used mass spectrometry, a leading method of identifying, quantifying and characterizing proteins to find proteins present in each of the 24 patient-derived xenografts of breast tumors of different subtypes. The team identified 10,000 proteins and their amounts across tumors.
In certain patient-derived xenografts of breast tumors with specific rogue proteins, targeting those proteins with specific inhibitors resulted in suppression of tumor growth in the model.
“A substantial number of these proteins identified in the xenograft model are potential targets for drugs,” Ellis said. “In addition, similar protein signatures were observed in breast cancer samples from patients, which suggests our approach has potential clinical relevance.”
The study was published in Nature Communications.
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