Dr. Bo Xu and his team at Southern Research are exploring exactly how the building block of life, DNA, plays a central role in cancer-cell formation and how penetrating these molecular pathways can produce new, lifesaving treatments.
Developing a complete picture of processes such as tumorigenesis and how to block the ingenious defense mechanisms of these cells will lead to cures, said Xu, M.D., Ph.D., who heads the organization’s Cancer Research Program and chairs its Oncology Department.
“Typically, when the tumor starts, your body’s immune system can recognize that something is going wrong with a cell,” he said. “It will attack that cell and can eliminate it. That’s a normal immune system response. But tumor cells are very smart – they actually produce a protein that fools the immune system, so they evade the normal immune response.
“At Southern Research, we’re working on a strategy to prevent the tumor cells from evading the immune system response,” Xu added.
His research primarily focuses on the mechanisms of how DNA repairs itself after exposure to damaging ionizing radiation, chemicals, cigarette smoke, or another kind of assault. He also is seeking to develop molecularly targeted drugs to enhance cancer treatments.
“What’s interesting is to know how normal cells become a tumor cell, when they start and how they progress, and how we can prevent that progress,” Xu said. “Also, we want to know how tumor cells respond to treatment when we use radiotherapy and chemotherapy, and whether we can improve the therapeutic outcome of those treatments.
“Everything is focused on DNA,” he added.
While scientists know a lot about how cancer genes work, many tumors simply cannot be linked to a specific gene. Most likely, cancer stems from more than one gene mutation, which can affect the production of proteins that swarm around the genes to repair damage. This disruption of the repair system can clear the path for a tumor to form.
“We still have a lot of unknowns,” Xu said. “Right now, the challenge is that we can look at one particular pathway from A to B to C, and we know that in many cases, these particular things contribute to tumorigenesis, but we don’t know how these 20,000 proteins work together.”
The DNA damage response, in particular, holds important clues about how to attack cancer more effectively, he said.
“We know that damage to the DNA can trigger cancer, but we know less about how cells deal with the damage. You see, the damage is happening all the time, every minute. But how cells deal with damage is more important. To repair it, we have to recognize how the damage is taking place.”
One approach is to stimulate a better DNA repair mechanism in normal tissues that could actually prevent a tumor from gaining a foothold.
“If the cell is damaged beyond repair, the body has to get rid of it.
That’s actually one of the strategies now — to induce ‘program cell death’ in tumor cells and let them destroy themselves,” Xu said.
Another approach is to find a way to disrupt the cancer cells’ own DNA repair system at the molecular level.
“Tumors also use mechanisms, like normal cells, to repair the damage to the tumor cells’ DNA and become resistant to treatment,” he said. “If we understand how they do their work in a particular setting, then we might be able to inhibit the system so that they cannot repair the damage and be more vulnerable to treatment.”
Xu, who began his career as a radiation oncologist in China in 1998 and joined Southern Research 10 years ago, aims to build on the significant anticancer work done at the Birmingham-based organization, which began in the late 1940s.
Howard Skipper, Ph.D., who launched the cancer research program at Southern Research, is credited with developing effective anticancer chemotherapy treatments and demonstrating that therapies had to eradicate every cancer cell to ensure patient survival, among other things.
“Southern Research is one of the best places to do cancer research,” Xu said. “We’re fortunate to have had pioneering scientists, especially Skipper, who was instrumental in cancer chemotherapy. People didn’t believe that cancer could be cured by a drug, but he was the one who proved that.”
The work of Skipper’s team also laid the foundation for one of the nation’s most productive drug discovery programs. Southern Research has produced six FDA-approved anticancer drugs and another medicine that lessens the harmful effects of chemotherapy and radiation. In addition, its drug development labs have tested about 80 percent of oncology drugs for efficacy.
Xu remains inspired by the work of Skipper, who spent more than 40 years at Southern Research and won the Lasker Foundation Prize for basic medical research in 1974. A framed portrait of Skipper hangs in his office.
“I’m very fortunate to have the office that used to be occupied by Skipper,” he said.
Xu’s research has provided insights into the mechanisms of tumor cell sensitivity to radiotherapy, mechanisms of tumor metastasis, and molecular targeted approaches to radiosensitization. Learn more about Xu’s research.