Detection of Aberrantly Glycosylated Biomarkers as a Novel Approach to Diagnose and Monitor Breast Cancer
Abstract
There is currently no blood test to diagnose breast cancer or to effectively monitor a patient’s disease progression or response to treatment. The development of a reliable blood test to screen for and monitor breast cancer is urgently needed. Proteins with sugar structures attached are ideal to be used as cancer diagnostic markers because they are shed into the bloodstream and can be detected via a blood test. N-glycolylneuraminic acid (Neu5Gc) is a type of sugar structure that is not produced by healthy human cells, but can be produced by cancer cells. A test for Neu5Gc-containing breast cancer-specific markers in blood has not yet been developed because the tools needed to sensitively measure this sugar were not available. We have previously designed a sugar-binding protein called SubB2M. This protein can bind to and detect the cancer-associated sugar, Neu5Gc. We developed a test to measure Neu5Gc in human serum using our SubB2M protein combined with an instrument that can measure very small amounts of substances in fluids. This test is very sensitive and uses only 1/1000th of one mL of patient blood sample for each assay. Using our test, we found that breast cancer patient blood at all stages, from early to late stage, had increased levels of the Neu5Gc compared to healthy controls. These exciting findings have demonstrated that we can detect Neu5Gc in breast cancer patients and that this test may be a useful tool for early cancer diagnostics, as well as a tool for monitoring treatment and disease progression. The crucial question that remains to be answered is the identity of the blood proteins in patient serum that are attached to the Neu5Gc sugar. Identification of these breast cancer-associated proteins, that carry the Neu5Gc sugar we are detecting, has the potential to enable the development of clinically useful early-stage screening and monitoring tests for breast cancer patients and is the aim of our project. We will use our novel Neu5Gc-binding protein to capture low abundant tumor-derived marker candidates in the blood of breast cancer patients. We will then use analytic techniques to identify these markers and use this information to develop tests that not only detect increased levels of these markers but also detect the Neu5Gc sugar on the marker. Detection of the Neu5Gc sugar will distinguish between the marker derived from a tumor and the normal, healthy version of the marker. This type of test will reduce false positive results and help to address the overarching challenge of “Conquer the problems of overdiagnosis and overtreatment.” Even if we do not identify new breast cancer markers, we can use our concept to improve upon existing blood marker tests for breast cancer because levels of existing cancer markers are raised in non-cancer conditions, such as pregnancy. The successful completion of our project will result in a simple blood test that can be used to screen for breast cancer and can efficiently monitor a patient’s response to treatment and their disease. All women potentially affected by breast cancer will benefit from our discoveries. By diagnosing breast cancer as early as possible, patients can be treated before their disease progresses too far, which will address the overarching challenge of “Eliminate the mortality associated with metastatic breast cancer.” Also, by accurately monitoring the progression of a patient’s cancer and how they respond to their treatment, this will address the overarching challenge of “Distinguish deadly from non-deadly breast cancers.” If successful, the clinical implementation of our tests will result in increased survival rates and better outcomes for breast cancer patients, contributing to the Breast Cancer Research Program’s mission of ending breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010527
Entities
People
- Michael P. Jennings
Organizations
- Griffith University
- United States Army