What six letter word scares most folks?  Cancer.  Because it’s deadly and because we don’t know why some folks respond well to treatment- and others just don’t.

It’s why we’ve tried all sorts of cocktails (mixtures of drugs that can hopefully work better together), putting patients on oxygen while undergoing chemotherapy- pretty much any idea that presents merit.

Pancreatic cancer is one of the worst of them.  Because only 1 in 20 survive the diagnosis beyond the five year mark.  No matter the therapy.   Right now, the therapy of choice is gemcitabine.  This drug is used for other cancers, too.

Basically, this is a drug that is an analogue of cytidine, so the cells pick up portions of the gemcitabine during DNA replication, which then stops normal cell growth (apoptosis – cell death results) and usually arrests the continued growth of the tumor.  Gemcitabine also attacks RNR (ribonucleotide reductase), which inactivates the enzyme, so DNA replication is difficult, yielding another avenue towards apoptosis.

Given these facts, we would assume that gemcitabine would be 100% effective against pancreatic cancer.  But, it’s not.  So, Dr. Timothy Yen (Temple University), along with his two post-docs, Drs. Vikram Bhattacharjee and Yan Zhou, set out to find why that is so.  They presented their results, A synthetic lethal screen identifies the Vitamin D receptor as a novel gemcitabine sensitizer in pancreatic cancer cells, in the journal Cell Cycle.

While the title says it all, the approach was pure brute force. The researchers removed the 24000 genes present in the pancreatic cancer cells and flooded them with gemcitabine. The gemcitabine was effective only when the genes were turned off.  And, when the gene that binds to vitamin D was turned off (“knocked out” is a term they used), the chemical was extremely effective.

This was interesting, since while vital for health, vitamin D is normally just a primary need for bone health and growth.   Not so for general cell growth.  But, obviously, pancreatic cancer is not normal cell growth- and it certainly does need vitamin D.    It seems that vitamin D provides for the cell repair after chemo- so making the vitamin D unavailable means the drug remains effective against cancer.

So, now the trick is to find ways to deactivate the vitamin D receptors in pancreatic cell cancers.  Because if we do that, then our drug regimens will be more effective against pancreatic cancer.  That’s really good news, because there are plethora of drugs that interact with vitamin D receptors.

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