Reducing Chemo Side Effects by Exploiting Tumor Cell "Doors"

Results from the DoD's Era of Hope Conference

Yesterday we looked at the challenges of delivering next generation peptide drugs to breast tumors. Today we'll continue to talk about the importance of drug delivery, but in the context of chemotherapeutics, by looking at more research coming out of this week's Era of Hope conference in Orlando.

Drs. Andras Lacko and Nirupama Sabnis from the University of North Texas Health Science Center in Fort Worth showed a technology that could potentially improve the efficacy and decrease the side effects of any chemotherapy drug.

Chemotherapy drugs are by definition poisons. So ideally you want them to enter tumor cells and not healthy cells where they can do things like cause hair loss and worse. But how to accomplish this?

Here's how: find a molecular "door" that only exists on tumor cells -- or that exists in much greater abundance on tumor cells compared to healthy calls.

This is what our featured research team did.

They found that a certain cell surface receptor called "scavenger receptor type B1" (SR=B1) is much more prevalent on tumor cells. This receptor's function on healthy cells is to extract a portion of circulating HDL cholesterol molecules needed for normal cell processes. But since tumor cells grow and proliferate much more rapidly than normal cells, they need much more of this HDL cholesterol element. So tumor cells put many more of these HDL-grabbing SR=B1 receptors on their surface.

So there it is! Our door!

The researchers exploit this door by creating so-called "rHDL nanoparticles" containing drugs of interest. A nanoparticle is an aggregate (a grouping) of defined molecules. In this case, the main component of the nanoparticle is rHDL. The "r" stands for "reconstituted." The other component is the drug of interest. The goal is to trick the cell's SR-B1 receptors into pulling the drug-containing nanoparticles into the cell.

And that's what happens. In Drs. Lacko and Sabnis' research they tricked tumor cells in mice to pull in a drug that isn't a standard chemotherapeutic. But as they said at the conference, "This novel drug delivery system has the potential to be compatible with most of the commonly used chemotherapy agents."

You might recognize that this drug delivery model has similarities with Abraxane, the "nanoparticle albumin-bound" version of the chemotherapeutic Taxol (paclitaxel) that is FDA-approved for the treatment of breast cancer. In the case of Abraxane, the protein used in the nanoparticle is albumin, which tends to attach to albumin receptors in blood vessels around tumors.

So this concept of creating protein-chemo nanoparticles seems to be gaining momentum.

Next the University of North Texas researchers are going to look at replacing the rHDL with a smaller protein, or peptide, that is known to mimmick HDL and which is currently used and approved for the treatment of arteriosclerosis. This would make any future drug easier to get through regulatory approval and likely less expensive.

My thanks to Dr. Sabnis for speaking with me yesterday about her research.