New discovery shows promise against pancreatic cancer

WASHINGTON - Johns Hopkins scientists have made a new discovery that could be helpful in the fight against pancreatic cancer.

By determining what goes missing in human cells when the gene that is most commonly mutated in pancreatic cancer gets turned on, scientists have discovered a potential strategy for therapy.

The production of a particular cluster of genetic snippets known as microRNAs is dramatically reduced in human pancreatic tumor cells compared to healthy tissue, according to the study.

When the team restored this tiny regulator, called miR-143/145, back to normal levels in human pancreatic cancer cells, those cells lost their ability to form tumors.

The team focused its investigation on KRAS, a member of the important RAS family of oncogenes that is mutated in almost all cases of the most common form of pancreatic cancer.

The researchers conducted their studies in a multitude of model systems - human cells growing in culture as well as those harvested directly from tumors, and also in mice and zebrafish.

First, using cell lines derived from pancreatic tumors and growing in culture, they added gene products such as mutant KRAS and an inhibitor of mutant KRAS, and then measured the microRNA responses.

Next, they conducted the same experiments using cells from patients’ pancreatic tumors. Finally, they looked at pancreatic tissue from mice and zebrafish to see what happened when KRAS was activated.

Every time, the team noted the same robust findings. When KRAS was activated, the microRNA cluster miR-143/145 was powerfully repressed, to a fraction of the levels in normal, non-cancerous cells.

Restoring the expression of miR-143/145 back to the level of normal cells was sufficient to confer “a very striking change in behavior of those cells,” said Josh Mendell from Johns Hopkins University School of Medicine.

The study has been published in Genes and Development, Dec. 15. (ANI)