MAR 29, 2017 6:34 PM PDT

Personalizing Breast Cancer Treatments by Targeting Specific Proteins

WRITTEN BY: Carmen Leitch

One of the major aims of biomedical research is to improve patient therapy, and as more powerful research and clinical tools have become available, therapeutics that are tailored to individual patients has become a more realistic goal. Scientists have now developed a method for a more personalized approach to breast cancer treatment, by both targeting the proteins that help drive tumor growth and evaluating the efficacy of drug treatments that act upon those drivers. The work, which was reported in Nature Communications, is summarized in the following video.

"Here we study the problem of how to design more effective cancer treatments with a two-pronged approach," commented one co-author of the report, Dr. Matthew Ellis, Professor and Director of the Lester and Sue Smith Breast Cancer Center at Baylor. "We combine patient-derived xenografts and proteogenomic integration." Patient-derived [tumor] xenografts are created by implanting a sample taken from a human cancer tumor into a lab mouse, specifically one that is immunodeficient to minimize transplant rejection.

"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," explained Ellis. "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."

It’s known that cancer cells express different genes than normal cells do, which leads to differential protein expression as well. Previous research has demonstrated that this method creates a good model; patient-derived xenografts of breast cancer tumors demonstrate a gene and protein expression profile that is like that seen in the original breast tumors. In addition, these xenografts seem to react to drug treatments on ways that are similar to what is observed in the tumors of human patients.

"Proteins carry out most of the biological functions in the cell," said Dr. Li Ding, an 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."

For this work, the investigators utilized mass spectrometry, which is a common technique that can quantify and characterize proteins to identify the proteins present in 24 different patient-derived xenografts of breast tumors of various subtypes. The research team found and measured the levels of 10,000 proteins in each of the tumors. 

The next step was to test therapeutics; in some patient-derived xenografts of breast tumors specific dysfunctional proteins were targeted by specific inhibitors. The researchers were successful; they observed a reduction of tumor growth in the disease model. 

Illustration of generation and proteogenomic characterization of breast cancer xenograft models. / Credit: Nature Communications Huang et al 2017

"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." 

He expanded on how this idea can be applied to personalized medicine. “Eventually, with this new approach scientists will be able to answer questions such as why a certain drug that induced one tumor to shrink in one patient did not affect the growth of a similar tumor in another patient,” Ellis said. “The idea behind this approach is to find out what are the driving pathways of each person’s cancer. Once we know these pathways, the next step is to use drugs to interrupt these pathways and lead to outcomes that are better than giving patients non-specific therapy. The mouse work is promising enough to adapt these technologies for real time analysis of patient samples so that clinical trials can be designed to test this new diagnostic and drug selection approach. The National Cancer Institute has agreed to invest in this next phase of the project.”

 

Sources: UPI, Baylor College of Medicine, Nature Communications

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAR 11, 2020
Cell & Molecular Biology
MAR 11, 2020
Generating Human Tissues in Space
Researchers from the University of Zurich are studying how weightlessness impacts the production of human tissue.
MAR 23, 2020
Cell & Molecular Biology
MAR 23, 2020
How a Father's Diet Can Impact the Health of His Offspring
When fathers consume a diet high in fat or low in protein it can increase the risk of metabolic disorders like diabetes ...
APR 21, 2020
Neuroscience
APR 21, 2020
Considerations for Lab Managers in Choosing a Microplate Reader
In today's high-tech, digitized laboratory environments, nobody pays very much attention to the humble plastic micro ...
APR 21, 2020
Cell & Molecular Biology
APR 21, 2020
Virtual Cell Provides a Close Look at Gene Expression During Development
Living organisms start out as one cell, and its genetic programs allow it to divide many times over, to give rise to the ...
MAY 20, 2020
Clinical & Molecular DX
MAY 20, 2020
QMS Competencies Your Reagent Supplier Should Possess
The ability of a clinical laboratory to provide consistent and reliable results to their customers depends on the consis ...
MAY 26, 2020
Immunology
MAY 26, 2020
The Hunt for Rare Immune Cells, to InfinityFlow and Beyond
The immune landscape is staggeringly complex, with a myriad of genetically and functionally distinct immune cell subpopu ...
Loading Comments...