Agents and methods for treating pancreatic ductal adenocarcinomas
AssigneeThe General Hospital Corporation
InventorsRaul Mostoslavsky, Sita Kugel, Anders M. Naar
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Abstract
It has been discovered that NAD+-dependent histone deacetylase SIRT6 is critical for suppression of PDAC by controlling 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.
Claims5
A method of diagnosing and treating pancreatic ductal adenocarcinoma (PDAC) in a subject, the method comprising:
- providing a sample comprising pancreatic cells from the subject;
- performing an assay to determine a level of Sirtuin 6 (SIRT6) expression in the sample;
- comparing the level of SIRT6 expression in the sample to a reference level of SIRT6 expression;
- identifying a subject who has a level of SIRT6 expression in the sample below the reference level as having PDAC or having an increased risk of developing PDAC;
- and
- administering a therapeutically effective amount of a let-7g mimetic to the identified subject who has a level of SIRT6 expression in the sample that is below the reference level.
Dependencies are inferred from the claim text.