The cancer glycocode as a family of diagnostic biomarkers, exemplified by tumor-associated gangliosides

One unexploited family of cancer biomarkers comprise glycoproteins, carbohydrates, and glycolipids (the Tumor Glycocode).A class of glycolipid cancer biomarkers, the tumor-marker gangliosides (TMGs) are presented here as potential diagnostics for detecting cancer, especially at early stages, as the biological function of TMGs makes them etiological. We propose that a quantitative matrix of the Cancer Biomarker Glycocode and artificial intelligence-driven algorithms will expand the menu of validated cancer biomarkers as a step to resolve some of the challenges in cancer diagnosis, and yield a combination that can identify a specific cancer, in a tissue-agnostic manner especially at early stages, to enable early intervention. Diagnosis is critical to reducing cancer mortality but many cancers lack efficient and effective diagnostic tests, especially for early stage disease. Ideal diagnostic biomarkers are etiological, samples are preferably obtained via non-invasive methods (e.g. liquid biopsy of blood or urine), and are quantitated using assays that yield high diagnostic sensitivity and specificity for efficient diagnosis, prognosis, or predicting response to therapy. Validated biomarkers with these features are rare. While the advent of proteomics and genomics has led to the identification of a multitude of proteins and nucleic acid sequences as cancer biomarkers, relatively few have been approved for clinical use. The use of multiplex arrays and artificial intelligence-driven algorithms offer the option of combining data of known biomarkers; however, for most, the sensitivity and the specificity are below acceptable criteria, and clinical validation has proven difficult. One strategic solution to this problem is to expand the biomarker families beyond those currently exploited. One unexploited family of cancer biomarkers comprise glycoproteins, carbohydrates, and glycolipids (the Tumor Glycocode). Here, we focus on a family of glycolipid cancer biomarkers, the tumor-marker gangliosides (TMGs). We discuss the diagnostic potential of TMGs for detecting cancer, especially at early stages. We include prior studies from the literature to summarize findings for ganglioside quantification, expression, detection, and biological function and its role in various cancers. We highlight the examples of TMGs exhibiting ideal properties of cancer diagnostic biomarkers, and the application of GD2 and GD3 for diagnosis of early stage cancers with high sensitivity and specificity. We propose that a quantitative matrix of the Cancer Biomarker Glycocode and artificial intelligence-driven algorithms will expand the menu of validated cancer biomarkers as a step to resolve some of the challenges in cancer diagnosis, and yield a combination that can identify a specific cancer, in a tissue-agnostic manner especially at early stages, to enable early intervention.