Figure 1.

Neoantigens generated by modifications at DNA, RNA, and protein levelsas well as by PTMs

Cancer cells frequently express unique protein species that are not present in healthy tissues (neoantigens), holding tremendous potential for targeted therapies and immunotherapy. Neoantigens may derived primarily from alterations in genome but also in RNA processing and other events underlying protein synthesis. Protein maturation with PTMs, such as glycosylation and phosphorylation, adds a second layer of specificity, which is valuable toward more effective targeted therapeutics. Beyond genetic alterations, epigenetic regulation plays a key role in governing gene expression as well as processing, significantly contributing to the formation of a wide array of proteoforms either directly or indirectly modulating the expression of enzymes involved in PTMs of proteins. Me, methyl; Ac, acetyl; SLe^A, sialyl-Lewis A; SLe^X, sialyl-Lewis X; S3T, sialyl-3-T; STn, sialyl-Tn; GPI, glycosylphosphatidylinositol; PTM, post-translational modification.