New Treatment Goes After Notoriously Tough Cancer Stem Cells

11/25/2013

Cancer is not a single disease, and different types of cancers vary significantly in how difficult they are to treat. Some cancers are relatively easy to address with conventional chemotherapy and radiation, whereas others are either non-responsive to such treatments or quickly develop resistance to available options. In the second circumstance, even if initial treatment appears to be successful, a recurrence can be devastating – when the medicines that worked so well the first time fail to have a significant effect.

As such, doctors and scientists are constantly looking for new ways to fight cancer. One such method involves the use of targeted toxins, poisons designed in such a way that they primarily or only bind to cancerous cells. Such specificity not only reduces side effects associated with conventional treatments, it potentially makes it more difficult for resistance to evolve.

One type of targeted toxin that has already been used to safely and effectively treat several kinds of human cancer is known as a bispecific ligand-targeted toxin, or BLT. BLTs contain a toxin linked to two different target molecules, where receptors for both of those targets are usually located on the cancer cell designated for attack. Using two molecular targets at the same time increases the specificity of the poison, making it less likely to go after non-cancerous cells than monospecific toxins, which only contain a single target. 

Canine hemangiosarcoma (HSC) is relatively common in companion animals. It is also relatively difficult to treat, as they quickly become resistant to conventional forms of therapy. Because of this, a group of scientists from the University of Minnesota wondered if BLTs might be an effective way of addressing these cancers. With support from the AKC Canine Health Foundation, they investigated whether cells derived from HSCs could be killed off by a BLT consisting of a deimmunized Pseudomonas exotoxin (PE) linked to epidermal growth factor and urokinase.

The results were quite promising. The BLTs were capable of killing not only cells derived from HSCs, but cultured hemangiospheres.  Such spheres bear a strong resemblance to cancer stem cells, which are notoriously difficult to treat. However, even in those more complicated circumstances, the BLTs mounted an effective attack. It took higher concentrations to kill off the CSCs than the other cells, but the amount of toxin necessary was still within the bounds of safety.

The study, published in the International Journal of Cancer, isn’t only good news for dog owners and dog lovers. Canine HSC is quite similar to a human cancer known as idiopathic angiosarcoma. Not only is idiopathic angiosarcoma aggressive and similarly difficult to treat, it’s rare enough to make researching a cure difficult. However, it seems likely that a treatment for canine HSA will also work on the related human cancer, and the canine cancer is common enough that research on it is much easier to advance.

This work was funded by AKC Canine Health Foundation grant 1131.

Publication:

Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors; Schappa JT, Frantz AM, Gorden BH, Dickerson EB, Vallera DA, Modiano, JF.; International journal of cancer. 2013 Oct 15;133(8):1936-44.

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