It has been discovered that NAD+-dependent histone deacetylase SIRT6 is critical for suppression of PDAC by con trolling the expression of Lin28b, which is a negative regulator of let-7 microRNA. Specifically, SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This invention relates generally to agents and methods of reducing expression or activity of Lin28b to treat (aggressive) PDAC in a subject.

The present invention discloses methods, for differentiating between normal or reactive cells and malignant cells biological samples comprising: exposing the biological sample to an antibody to L523S protein and detecting the presence of the antibody bound to L523S protein within the malignant cells. In embodiments, such methods may further comprise: exposing the biological sample to an antibody to a second protein that is a marker of cell lineage and detecting the presence of the antibody to the second protein within cells corresponding to a particular cell lineage and/or may comprise: exposing the biological sample to an antibody to a third protein which is a marker of cells that are normal or reactive and detecting the presence of the antibody to the third protein within cells that are normal or reactive.

The present invention discloses methods for differentiating between normal or reactive cells and malignant cells in biological samples comprising: exposing the biological sample to an antibody to L523S protein and detecting the presence of the antibody bound to L523S protein within the malignant cells, in embodiments, such methods may further comprise: exposing the biological sample to an antibody to a second protein that is a marker of cell lineage and detecting the presence of the antibody to the second protein within cells corresponding to a particular cell lineage and/or may comprise: exposing the biological sample to an antibody to a third protein which is a marker of cells that are normal or reactive and detecting the presence of the antibody to the third protein within cells that are normal or reactive.