Ganglioside as a Therapy Target in Various Types of Cancer

Abstract

Since their discovery in 1940, it has been well established that gangliosides are associated with a number of biological pathways and cellular processes such as growth, differentiation and toxin uptake. Gangliosides are glycosphingolipids containing neuraminic acid which are expressed on the plasma membrane of cells particularly in the nervous system. Heterogeneity and structural variation in the carbohydrate chains of gangliosides contributes to unique features of each of these molecules. Thirty five years ago it was discovered that aberrant glycosylation occurs in a variety of human cancers, including aberrant glycosylation of gangliosides. Ganglioside expression in terms of quality and quantity varies in different cancers and different roles may be played. Gangliosides, by affecting the immune system, including esxpression of cytokines and adhesion molecules, may inhibit anti-tumor mechanisms, as well as having direct impact on angiogenesis, cell movement and metastasis. It should be noted that different kinds of gangliosides do not all act by the same mechanisms.

Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

“…As mentioned previously, gangliosides found on the plasma membrane have been implicated in oncogenic signaling [ 193 , 194 ] and thus have been proposed to be useful targets for cancer treatment [ 195 ]. While one recent study suggests that targeting O‐Acetyl‐GD2, a derivative of GD2 ganglioside in which the outer sialic acid residue is modified by an O‐acetyl ester, might be helpful in treating chemoresistant glioma cells, particularly if used in combination with other drugs [ 196 ], most studies have focused on the modulation of GM3 metabolism as a means to address chemoresistant cancer cells.…”

Characterization of Glycosphingolipids and Their Diverse Lipid Forms through Two-Stage Matching of LC-MS/MS Spectra

“…7 Therefore, GSLs are directly involved in signal transduction, 8 cell division, recognition, adhesion and apoptosis, 9,10 and embryonic and nerve system development. 11−13 In addition, abnormal GSL expression and metabolism are correlated to many diseases, such as cancer 14,15 and Alzheimer's disease. 16,17 Because of their biological significance, GSLs have been a major research focus across different disciplines, among which GSL structural analysis is especially imperative.…”

“…GSLs are an essential component of the cell membrane and a key player in various biological and pathological processes. − For example, GSL is the main form of glycoconjugates in vertebrate brains, where >80% of the glycans in the cell glycocalyx are glycolipids . Therefore, GSLs are directly involved in signal transduction, cell division, recognition, adhesion and apoptosis, , and embryonic and nerve system development. − In addition, abnormal GSL expression and metabolism are correlated to many diseases, such as cancer , and Alzheimer’s disease. , Because of their biological significance, GSLs have been a major research focus across different disciplines, among which GSL structural analysis is especially imperative. Studies on GSLs expressed by various cells/tissues (i.e., glycolipidomics analysis) to reveal abnormal GSL expression would not only help gain a deeper understanding of the functions and action mechanisms of GSLs in various processes but also help identify new markers useful for disease diagnosis and therapy.…”

BR2 cell penetrating peptide effectively delivers anti-p21Ras scFv to tumor cells with ganglioside expression for therapy of ras-driven tumor

“…Approximately 75% of primary and metastatic melanomas can detect GS [ 7 ]. GS is also highly expressed in other tumors, including osteosarcoma [ 8 ], small cell lung cancer [ 9 ], liver cancer [ 10 ], pancreatic cancer [ 11 ], gastric cancer [ 12 ], B-cell lymphoma [ 13 ], breast cancer [ 14 ], and bladder cancer [ 15 ].…”