Over the last decade, there has been an explosion in the amount of data generated from the DNA and RNA sequencing studies. Essentially, these data inform us about the blueprints of the cancer cell – the instructions it uses to carry out its primary function of cellular proliferation. However, translating these findings into new therapies has, with a few exceptions, proven to be very difficult. This is in part due to the fact that the instructions are many steps removed from the way that a cancer cell actually behaves. To help complete the cancer biology picture, researchers are increasingly turning toward mass spectrometry based proteomics.
Proteins make up the structure and moving parts that do the work of cells. Proteomics is the study of all the proteins present in a given tissue compartment such as: the blood, an organ, a tumor, or a bodily fluid. Studying the proteins present in different tissue types or in tissues under different conditions yields information about the nature of the cells in those tissues. When applied to cancer research, proteomics often takes the form of comparing the proteins present in tumors to those present in comparable normal tissues or comparing different molecular subgroups of a cancer type. There are a number of proteomics approaches applicable to different types of studies.
- Quantitative Proteomics: The most useful type of proteomics for biological studies is quantitative proteomics in which a mixture of unknown proteins can be simultaneously identified and quantitated. There are a number of different platforms for this including metabolic labeling and mass tagging.
- Targeted Proteomics: In this form, the proteins being sought are known and the assay is designed to provide maximum sensitivity. These assays often employ synthetic labeled peptides (protein fragments).
- Functional Proteomics: In this form, assays are designed to isolate proteins with specific modifications known to affect their activity such as phosphorylation. This data can then be used to construct maps of active pathways in a tumor.
- Proteogenomics: Cancer cells have many alterations to their DNA and some of these alterations can result in the creation of abnormal proteins that are unique to the tumor cell. By starting with DNA/RNA sequence information, one can identify the cancer cell’s proteins and match them to the altered DNA of that specific tumor in order to find those proteins that are specific to that tumor. These can be investigated for their functional activity, ability to be targeted by the immune system and as detectable biomarkers.
Proteomics is a rapidly evolving field due to advances in mass spectrometry allowing higher throughput and greater accuracy. The addition of proteomics to genomics will help investigators translate genomic findings into new therapies for children with brain tumors.
Written by Brian R. Rood, MD, a neuro-oncologist and cancer researcher at Children’s National Hospital and Children’s National Research Institute.
This article was written for the Childhood Brain Tumor Foundation, Germantown, Maryland, www.childhoodbraintumor.org. 2020.
