Molecular signature tied to more aggressive pancreatic cancer

Last Updated: 2016-05-19

By Megan Brooks

NEW YORK (Reuters Health) - Boston-based researchers have identified a molecular signature in pancreatic ductal adenocarcinoma (PDAC) tumors that is associated with more aggressive cancer and poorer prognosis.

Hallmarks of the signature are reduced expression of SIRT6, a protein involved in glucose metabolism, increased expression of Lin28b, an oncoprotein normally expressed during fetal development, and reduced expression of the tumor-suppressor let-7.

"Not only did more than a third of analyzed PDAC patient samples exhibit the molecular signature we identified, those patients also turned out to have very poor prognoses," senior author Dr. Raul Mostoslavsky, of the Massachusetts General Hospital Cancer Center and Harvard Medical School, said in a news release.

Dr. Mostoslavsky added in email to Reuters Health that based on these findings and experiments in cells and mice "it is predicted that inhibition of Lin28b in those patients could selectively and efficiently target the cancer cells, providing a novel clinical target for these subtypes of PDACs."

The study is available online now in the journal Cell.

"A general message from these studies is that cancer cells benefit from modulating epigenetic factors like SIRT6 by acquiring the ability to override normal cellular growth control patterns," Dr. Mostoslavsky further explained in the news release. "Each tumor type may acquire a unique set of capabilities that may provide tumor-specific growth and survival advantages, which may need to be determined for each kind of cancer."

"In terms of our findings regarding PDAC, we are intrigued by the downstream pathways controlled by Lin28b and how they increase aggressiveness and metastasis, and we are hopeful that developing in the future Lin28b inhibitors could benefit this subset of PDAC patients, who currently have very few treatment options," Dr. Mostoslavsky added.

Looking ahead, Dr. Mostoslavsky told Reuters Health, "The immediate follow-up for us is trying to understand why lack of SIRT6 makes these tumors more aggressive. In particular, why these mice exhibit a significant increase in metastasis. Is this phenotype related to a de-differentiation program (driven by the oncofetal protein Lin28b), and if so, how is that program increasing metastases."

The study had no commercial funding and the authors have disclosed no relevant conflicts of interest.

SOURCE: http://bit.ly/1Xzotuo

Cell 2016.