VCU news

By Blake Belden
VCU Massey Cancer Center

A decade ago, VCU Massey Cancer Center researcher Charles Clevenger, M.D., Ph.D., was studying a hormone linked to the development of breast cancer when he identified a specific enzyme that contributes to the spread of tumor cells. The logic quickly unfolded that if you block this enzyme, you could potentially develop a novel treatment for breast cancer.

A biopharmaceutical company reached out to Clevenger and told him they had a unique set of compounds that could disrupt the function of this enzyme. Early results in Clevenger’s lab found the experimental drug successfully killed cancer cells. But he soon encountered a massive roadblock.

“The drug company that gave me the compounds called me and said they didn’t have complete ownership of the intellectual property and they wanted the drug back,” said Clevenger, a member of Massey’s Developmental Therapeutics research program and the Carolyn Wingate Hyde Endowed Chair in Cancer Research at Massey. 

“We had just demonstrated this drug killed breast cancer cells and written multiple grants for additional studies, but all of a sudden our research screeched to a dead halt,” he said.

For the better part of a decade, Clevenger, chair of the Department of Pathology at the VCU School of Medicine, was unable to continue his research because there was no way to acquire the drug. Now he will finally be able to continue this research thanks to a new Massey collaboration with a world-class drug synthesis laboratory at Virginia Commonwealth University.

Developing Medicines for All

Established in 2017 within the VCU College of Engineering, the Medicines for All Institute at VCU is equipped to manufacture large volumes of targeted therapeutics for the university to conduct research. It also works on developing lower cost preparation methods for drugs associated with HIV, tuberculosis and malaria.

The institute’s inception goes back to 2007 when its CEO, Frank Gupton, Ph.D., retired from a career in the pharmaceutical industry and took a position at the university. He was asked to fill a new role that would help build a bridge between the fields of chemistry and chemical engineering. After returning to the workforce, this bridge led to what is now the VCU Department of Chemical and Life Science Engineering. Gupton became department chair in 2015.

Through a series of grants received in his early tenure at VCU, Gupton discovered a new method to manufacture a particular HIV drug that radically lowered the cost of production and price in the marketplace.

“Most pharmaceutical processes generate a huge amount of waste. Typically, to generate 1 kilogram of the active ingredient for a drug, you generate several hundred kilograms of waste,” said Gupton, who is also a member of the Developmental Therapeutics research program at Massey Cancer Center and the Floyd D. Gottwald Jr. Chair in Pharmaceutical Engineering at VCU.

For the initial HIV drug target, the amount of waste generated was approximately 60 kilograms per kilogram of product. The new process developed by Gupton generates only 4 kilograms of waste. This led to an increase in use of the drug in the global marketplace and a decline in the cost by around 40%.

Because of this success, the Bill & Melinda Gates Foundation awarded Gupton $40 million to recruit additional scientists to the university who could help synthesize multiple drugs at the same time, paving the way for what is now Medicines for All.

“Between the significant investments that the university has made to boost our infrastructure and the contributions made by the Gates Foundation, Medicines for All is uniquely poised to be able to conduct a lot of innovative science that’s going to help drive down the cost of health care — particularly global health care — and help advance some of the research initiatives on our medical campus here at VCU,” Gupton said.

Between the significant investments that the university has made to boost our infrastructure and the contributions made by the Gates Foundation, Medicines for All is uniquely poised to be able to conduct a lot of innovative science that’s going to help drive down the cost of health care

Synthesizing compounds for cancer research

One goal of Medicines for All is to reduce global health care costs. Another way it can have a tremendous impact is by providing scientists with drugs they need for research. Medicines for All can make drugs for research purposes that already hold Food and Drug Administration approval but are hard to obtain, drugs in development that don’t yet hold FDA approval, and entirely novel chemical entities that can be made from scratch at VCU.

For Massey researchers challenged by the barriers of accessing certain cancer drugs, they can now tap into a new resource.

“We’re working with Massey Cancer Center researchers to identify and synthesize those drugs so they can have direct access to them and be able to make cutting-edge discoveries using new technologies and new therapies that they normally wouldn’t have access to,” Gupton said. 

The structural compositions for many of the drugs being sought exist in the public domain, and the Drug Price Competition and Patent Term Restoration Act of 1984 (known as the Hatch-Waxman Amendments) allows organizations to produce a drug that is under patent if that organization isn’t planning to sell it.

Gupton recruited Keith Ellis, Ph.D., a member of the Developmental Therapeutics research program at Massey who has a background in oncology drug development and chemistry, to manage the collaborations between Medicines for All and Massey.

“By coupling Dr. Gupton’s drug synthesis powerhouse with Massey’s oncology research powerhouse, we have been able to implement an effective way for the cancer center to have access to molecules that it wouldn’t otherwise have access to, and to develop new drugs for targets that Massey researchers are already working on,” said Ellis, an associate professor in the Department of Medicinal Chemistry and a member of the Institute for Structural Biology, Drug Discovery and Development at the VCU School of Pharmacy.

“There is a real need for these drugs because a lot of times those compounds are exorbitantly expensive, the researchers need them in such large quantities, or the manufacturer wants to put conditions on supplying them,” Ellis said.

There is a real need for these drugs because a lot of times those compounds are exorbitantly expensive, the researchers need them in such large quantities, or the manufacturer wants to put conditions on supplying them

One area that Massey has been interested in expanding over the past several years is investigating novel chemical entities as opposed to reformulating old drugs for new purposes. However, researching new agents is often difficult because many pharmaceutical companies produce new compounds to conduct their own studies and are reluctant to share those materials with organizations that want to perform their own research, as Clevenger does at Massey.

Through collaboration with Ellis and Medicines for All, Clevenger was able to revive his abandoned research efforts.

“This collaboration is exciting for everybody. There are very few other cancer centers in the United States that have an entity like Medicines for All, and certainly not as well-funded or as creative as what we have here,” Clevenger said. “Medicines for All can provide new and existing compounds for a wide range of cancers, and allow us to answer questions that we previously couldn’t.”

Ellis said there are currently five collaborations with Massey that he hopes will be completed within the next six months, opening up availability for new projects.

“I constantly ask my colleagues and the folks at the Gates Foundation if anybody is doing this, and the feedback that I’m getting is there aren’t many people in the U.S. or around the world that are doing what we’re doing,” Gupton said.

I constantly ask my colleagues and the folks at the Gates Foundation if anybody is doing this, and the feedback that I’m getting is there aren’t many people in the U.S. or around the world that are doing what we’re doing

Fast-tracking advancements in cancer treatment

Massey is one of only 71 National Cancer Institute-designated cancer centers in the country, placing it in the top 4% of centers that receive federal funding and resources to lead and shape America’s cancer research efforts and make discoveries that become new treatments. One of Massey’s foremost goals is to take this designation a step further and earn NCI Comprehensive Cancer Center status, a classification awarded to the centers that demonstrate the highest ability to connect the scientific areas of basic, clinical and behavioral health research. This designation could attract additional funding, scientists and clinicians, fueling further innovations in research that would improve patient care.

Clinical trials are the last step on the long road to developing novel cancer treatments, and a cancer center’s ability to develop and conduct trials of all phases holds a big influence on its comprehensive cancer center standing.

Ellis hopes that collaborations through Medicines for All will accelerate Massey’s path to this designation, and is working to help initiate more phase 1 clinical trials.

“A large goal of our collaborations is to collect enough data on drug efficacy, but also to gather safety and toxicity data that allows us to then take that drug and produce enough of it to be used in clinical trials,” Ellis said.

Massey’s cancer center director, Robert Winn, M.D., is enthusiastic about the potential that Massey’s collaboration with Medicines for All holds for making new cancer discoveries.

“Massey’s partnership with Medicines for All gives our researchers a game-changing tool for facilitating the translation and advancement of their scientific discoveries from the laboratory into clinical trials,” Winn said. “Continuing to strengthen this unique collaboration will enhance and expedite Massey Cancer Center’s ability to develop novel therapies and bring them to cancer patients and our community.”