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Xiaoyang Qi, PhD
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Xiaoyang Qi, PhD
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Publish Date: 02/12/14
Media Contact: Cindy Starr, 513-558-3505
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Patients, Researcher Await Translation of Discovery Into Clinical Trial

Whenever Xiaoyang Qi, PhD, publishes a new paper or is interviewed by the media, the e-mails arrive in clusters from all over the world. Humble, hopeful and often desperate, they come from patients and family members eager to know when Dr. Qi’s discovery – a drug that has the potential to target multiple types of cancer – will be tested in a clinical trial for people.

"My hope is sooner, not later,” Dr. Qi says.

Dr. Xiaoyang Qi (pronounced ShawYung Chi) is a translational cancer researcher and associate professor in the division of hematology oncology, whose work straddles the UC Cancer Institute and the Brain Tumor Center at the UC Neuroscience Institute (both part of the UC College of Medicine and UC Health) as well as the Cincinnati Cancer Center, which includes the Cincinnati Children’s Cancer and Blood Diseases Institute.

He is internationally recognized for designing nanovesicles known as SapC-DOPS, short for saposin-C dioleoylphosphatidylserine, while working at Cincinnati Children’s Hospital Medical Center in 2002. SapC-DOPS is a drug that has been shown in preclinical studies to cause several types of cancer cells – including brain cancer cells – to self-destruct, without causing harm to healthy cells or tissues.

Still on the horizon is Phase I testing of the drug, which is manufactured as BXQ-350 by the Covington startup Bexion Pharmaceuticals. In 2013 Bexion received a rare $2.9 million Small Business Innovation Research Bridge Award from the National Cancer Institute, with Dr. Qi as co-Principal Investigator, to help it bring the drug into the clinical trial phase for patients with glioblastoma multiforme (GBM), the most common form of brain cancer.

Moving Beyond a Single Drug for a Single Target

The drug represents a departure from most targeting drugs, which go after one gene or one protein. "These therapies, when they move to clinical trials, expose a lot of limitations,” Dr. Qi says. "To me, a single drug aimed at a single target seems an insufficient way to manage a tumor. First of all, you have a limited fraction of patients who might benefit.

Secondly, cancer cells frequently resist the therapy by creating new mutations.” Even more problematic, Dr. Qi says, is the heterogeneity of tumors. "A single tumor in a single patient may consist of a variety of types of tumor cells, with different genetic background. So using a drug designed for only one type of mutation with a high level of expression may not affect cells with low-expression mutation within the same tumor mass. The unaffected cells can then revert to high-expression cells when the drug therapy is stopped.”

SapC-DOPS itself is a combination of two compounds that occur naturally in all human cells: 1) SapC, a protein that is contained in the lysosomes; and 2) DOPS, a phospholipid, known as dioleoylphosphatidylserine, that is contained in cell membranes.

The SapC-DOPS nanovesicle targets a lipid molecule called phosphatidylserine (PS) that has a ubiquitous presence on all cell membranes. In healthy cells, Dr. Qi explains, it is distributed asymmetrically, with greater abundance on the inside layer of the plasma membrane. But in viable cancer cells, its exposure is greatly increased on the outside of the cell membrane. This is true for cancers of the brain, pancreas, lung, breast, prostate and liver as well as for cancers that have metastasized from one part of the body to another. "I have about 100 cancer cell lines in my lab, and in all cases PS exposure is increased on the outer surface of the cell membrane,” Dr. Qi says.

While working in his lab at Cincinnati Children’s, Dr. Qi discovered something fascinating about SapC. The fusogenic protein, he realized, could induce fusion between the outside PS microdomains of cancer cell membranes and the nanovesicles. This could lead, therefore, to a cancer-selective targeting by SapC-DOPS.

Triggering a Cancer Cell's Demise

Dr. Qi subsequently found that SapC-DOPS had the ability to trigger the cancer cell’s death through a series of biochemical reactions after the membrane fusion. When these nanovesicles were injected into animal models of cancer, the results have been dramatic: a shrinkage or elimination of cancers in the body and also the brain. Research published last year in the journal Molecular Therapy and PLOS ONE showed that animal models of brain and pancreatic cancer that were treated with SapC-DOPS "experienced clear survival benefits.” The research established PS as a biomarker for brain and pancreatic cancer and SapC-DOPS as a potential biotherapy for brain and pancreatic cancer.

The promise of SapC-DOPS has riveted not only the American scientific community but also researchers and patients in China. Dr. Qi, who came to the United States from China in 1985, returns several times a year to work on parallel research with colleagues in Nanjing and Changzhou, Jiangsu province.

"There is a desperate need for new cancer drugs in China,” Dr. Qi says. "Because the population of China is so large, the number of cancer patients in absolute numbers is very high.”

In the e-mails Dr. Qi receives, desperate patients and families say they are willing to travel to the United States to participate in clinical trials. The better solution, he says, is for both countries to run the trials simultaneously. That day, he hopes, will not be too long in coming.

About Qi
• Title: Associate Director and Associate Professor, Division of Hematology/Oncology, UC College of Medicine

• Bachelor’s Degree: Nanjing University, 1982
• Doctoral Degree: Oklahoma State University, 1992
• Research Fellowship: Cincinnati Children’s Hospital Medical Center, 1996
• 2013 NIH funding: $305,799
• Nominee: 2014 Health Care Heroes, Innovator Category

This was originally featured in the UCNI blog.



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