of patients being seen in the clinic for a diagnosed brain tumor have
metastatic cancer, which has no treatment and detrimental outcomes in most
However, a new
Cincinnati Cancer Center (CCC) study, published in the advance online edition of the journal Oncotarget, provides hope that
previously studied SapC-DOPS could be used for treatment of brain cancer that
Xiaoyang Qi, PhD,
member of the CCC, associate director and associate professor in the division of
hematology oncology at the University of Cincinnati (UC) College of Medicine
and a member of the UC Cancer and Neuroscience Institutes and the Brain Tumor
Center, says this critical data shows promise for finding treatment for one of
the deadliest cancers.
A lysosomal protein
saposin C (SapC), and a phospholipid, known as dioleoylphosphatidylserine
(DOPS), can be combined and assembled into tiny cavities, or nanovesicles, to
target and kill many forms of cancer cells.
membrane-enclosed organelles that contain enzymes capable of breaking down all
types of biological components; phospholipids are major components of all cell
membranes and form lipid bilayers—or cell membranes.
Qi says his lab and
collaborators have previously found that the combination of these two natural
cellular components, called SapC-DOPS, caused cell death in cancer cell types,
including brain, lung, skin, prostate, blood, breast and pancreatic cancer,
while sparing normal cells and tissues.
"In spite of
significant advances in understanding of the biology of tumors in the body, the
translation of this knowledge to new and effective therapeutic strategies has
been slow,” he says. "As a consequence, brain tumors, either primary—known as
glioblastoma multiforme, the most aggressive and prevalent malignant brain
tumor—or secondary (metastatic), remain among the most untreatable and fatal of
He adds that brain
metastases arising from primary lung, skin and breast cancers affect about 10
to 30 percent of adult cancer patients and are much more prevalent than primary
targeted therapies are showing promising results, the difficulty in diagnosing and
effectively targeting micrometastases—multifocal small tumors that form as a
result of the primary tumor—makes the treatment of brain metastases one of the
most pressing challenges in clinical oncology,” Qi says, adding that it’s often
hard to both image the smaller tumors and to operate on them. "In this study, we
evaluated the ability of SapC-DOPS to selectively target brain metastases of
human breast and lung cancer cells in cultures and in animal models.”
Using two groups of
models—one injected with a placebo and the other injected with
SapC-DOPS—researchers found that those receiving treatment with the nanovesicles
had an extended life. Within the animal models, two were completely cured from the
brain tumor and resulting metastasis. Scientists were able to monitor the
uptake of SapC-DOPS by the tumors and their progression by using immunofluorescence
imaging of brain sections.
Within 24 hours of
injection, imaging showed that SapC-DOPS targeted the tumors and began to work.
tumors in these models were generated and did not arise naturally from primary
tumors, our models do not represent true metastases. However, they still reiterate
the essential steps of the metastatic process,” Qi says. "We were still able to
show the antitumor effects of SapC-DOPS on human brain tumor cells in models
and that SapC-DOPS selectively targets tumor cells in models with brain micrometastases
derived from human breast or lung cancer cells. We also showed that SapC-DOPS
has cytotoxic effects on metastatic breast cancer cells in cultures.
support the potential of SapC-DOPS for the diagnosis and therapy of primary and
metastatic brain tumors which is critically needed to increase survival rates
of patients with this illness.”
This work was
supported in part by a pilot grant from the UC Brain Tumor Molecular
Therapeutics Program, research funds and hematology oncology programmatic
support from the UC College of Medicine, as well as the National Institutes of
Health (1R01CA158372), and a New Drug State Key Project grant (009ZX09102-205).
Qi is listed as
an inventor on the patent for SapC-DOPS technology that is the subject of this