Virginia Commonwealth University

VCU Massey Cancer Center

Translational research: from bench to bedside

Maria Quigley, R.N., and Andrew Poklepovic, M.D., are conducting clinical trial studying a combination of chemotherapies for the treatment of advanced malignancies.

Since 1974, VCU Massey Cancer Center has been at the forefront of groundbreaking research to help save and improve the lives of those affected by cancer.  Bringing the latest discoveries to patients is the core of Massey’s mission. 

Massey’s science-driven translational research – moving scientific discoveries from the laboratory into real-world patient applications – is one of the many reasons the National Cancer Institute (NCI) recently awarded Massey a five-year renewal as one of only two NCI-designated Cancer Centers in Virginia. 

Often described as “bench-to-bedside” research, translational research involves several stages, including clinical trials, where consenting patients are given drugs, surgical procedures, devices or other interventions to treat cancer and are then closely monitored to determine side effects, effectiveness and other key findings. 

The four phases of clinical trials help provide scientists and clinicians with a variety of important information and data, from a drug’s dosage toxicity, for example, to side effects and patient benefits as well as risks. 

During Phase I trials, drugs are tested for the first time in small groups of participants in order to evaluate safety, to determine dose ranges and to identify side effects. 

Two of Massey’s Phase I trials have yielded promising results in the treatment of acute forms of leukemia and in cases of advanced malignancy such as breast cancer. 

Steven Grant, M.D., Olsson Chair in Oncology Research, associate director for translational research and co-leader of Massey’s Developmental Therapeutics program, is leading a research team studying the use of two targeted agents, belinostat (a histone deacetylase inhibitor, which acts by modifying the expression of genes involved in the regulation of cell differentiation and death) and bortezomib (a proteasome inhibitor that interferes with the cell’s ability to degrade unwanted proteins), for the treatment of acute leukemia. 

Funded in part by a highly competitive NCI $1.2 million “Grand Opportunities” award, the trial is a collaborative effort with M.D. Anderson Cancer Center in Houston, Texas, and H. Lee Moffitt Cancer Center in Tampa, Florida.  The preclinical findings from Grant’s lab studies at Massey showed that very low concentrations of the two agents used in combination were toxic to leukemia cells found in patients. Now in the Phase I clinical trial stage with principal investigator Beata Holkova, M.D., the research is designed to determine how participants tolerate various dose levels of the combination. Although still preliminary, results to date have been encouraging. 

“We’ve been able to translate our basic laboratory findings into the clinical arena and have had three patients who have either achieved or who have come close to achieving a complete remission,” Grant said. “That is not to say that the leukemia has been cured, only that at a certain point the leukemia was not detectable by standard means following treatment.” 

Such responses open up additional therapeutic options for leukemia patients, and point  the way toward promising outcomes. 

“Massey’s support of this research demonstrates the commitment of the institution to move laboratory findings forward to yield tangible benefits to patients,” Grant said. “It is an essential component of our success.”

Another example of Massey’s promising translational research involves the study of a different powerful drug combination. Principal investigator, Andrew Poklepovic, M.D., is leading the effort to study the use of pemetrexed (a multitargeted antifolate that prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells) and sorafenib (a multikinase inhibitor which works by slowing the spread of cancer cells) to treat advanced malignancies.

Originally co-developed by Massey scientist Rick Moran, Ph.D., Massey’s associate director for basic research, pemetrexed is now a leading medication for use in lung cancer treatment. Collaboration between Moran and Paul Dent, Ph.D., Universal Corporation Distinguished Professor in Cancer Cell Signaling, led to the discovery of additional anti-cancer applications for pemetrexed and even more anti-cancer benefits when the drug is used in combination with sorafenib. This combination explores a new strategy in fighting cancer known as toxic autophagy. 

“We’ve had a very good response in triple negative breast cancer, a disease that’s very difficult to treat and an area of real need,” Poklepovic said. Colon cancer, he added, may also be responding to the drug combination. “We frequently find that drugs working through one pathway or mechanism also work in other mechanisms. Pemetrexed’s alternate mechanism was found during Moran and Dent’s collaboration at Massey.” 

Because of the early and positive responses to breast cancer, the trial, which is funded entirely by Massey grants and philanthropic donations, has attracted additional support from the pharmaceutical industry in the form of drug contributions to the study. Such contributions can represent hundreds of thousands of dollars of a researcher’s budget.  “It wouldn’t have been possible to attract this additional support without the generosity of Massey and private donors,” he said. 

According to Poklepovic, many cancer centers have ideas that aren’t progressing to the trial level because of the lack of outside funding. When Massey sees a good idea, he said, external funding helps support the research. “And there are a lot of good ideas coming out of Massey.” 

Funding isn’t the only critical piece necessary for successful translational research.  At the center of all Massey research is the patient. Clinical trials wouldn’t be possible without volunteer participants who are willing to trust not only the scientific process, but also the team at the helm of such significant advancements in laboratory research and in clinical practice. 

“When we talk to patients, we explain that there are no guarantees,” said Mary Beth Tombes, R.N., clinical research nurse on Grant’s leukemia trial team. “We explain that we’ve had some good responses, but it still requires a leap of faith on the patient’s part.” 

That leap of faith resulted in remission for several participants in these two trials alone, and investigators are optimistic that there are more success stories to come. At Massey, more than 100 trials involving more than 20 types of cancer provide vital information for the continued development of new treatments. 

Many clinical trial participants make the decision to volunteer because of the opportunity to help themselves and to help others. Each works with and is monitored by a team of dedicated health care specialists including physicians, researchers, social workers, administrators and nurses, like Tombes. 

“It’s a real honor to care for people who are willing to participate in such an important process,” she said. “We go out of our way to make things easier for them. They are making a huge commitment to enhancing the body of medical knowledge and it’s an honor to be a part of that.” 

“This is how new discoveries are made,” said Poklepovic. “The hope for tomorrow lies in the things that are being developed now.”

Written by: Massey Communications Office

Posted on: September 17, 2012

Category: Research