June 15, 2016--As a professor of oncology and pharmacology, Anton Wellstein, MD, PhD, can see how rapidly his field is moving by how often he updates slides for the class he teaches at Georgetown’s medical school.
And lately, the frequency has picked up.
“It is fair to say that we have climbed almost to the top of a very big mountain,” he says. “And while we know there are many more peaks to climb, at least we are in a position to look at what lies ahead.”
Now, as the recently appointed deputy director of the Georgetown Center for Cell Reprogramming, Wellstein sees a clearer path to developing targeted therapies for a variety of cancers and their subtypes.
And it’s a revolutionary laboratory advance that Georgetown researchers made in 2011 that is paving the path forward.
A goldmine of information
Oncology has long had a resource unique to human disease, and the center maximizes that resource, Wellstein says.
“I always tell my students that they should go into cancer research because of a simple, yet profound, reason,” he says. “It is that people with cancer are happy, really delighted, to give you their diseased tissue. It isn’t possible to take bits of a disordered brain or diseased heart or other organs from patients to study.”
The actual diseased tissue — the tumor — is a goldmine of information on what powers cancer development and growth, Wellstein says.
Change in behavior
But the technique still widely used has problems. Researchers have developed therapies using hundreds and hundreds of cell lines that have been generated originally from human cancers.
“As precious as those laboratory cells are, they poorly reflect the disease occurring in an individual patient,” Wellstein says.
“These laboratory cells have adapted to conditions in the lab, so they have changed their behavior,” he adds.
But Georgetown’s Center for Cell Reprogramming offers a unique alternative, Wellstein says.
Reading the molecular blueprint
GUMC researchers, led by Xuefeng Liu, PhD, and Richard Schlegel, MD, PhD, worked out a way to produce conditionally reprogrammed cells (CRC) so that cancer cells, taken fresh from a patient, are treated and “fed” in such a way that they can stay alive indefinitely in laboratory conditions.
The cells that make up the tumor can be expanded as needed.
Researchers can then “read” the molecular blueprint of an individual patient’s tumor and test therapies to see which are best at killing the cancer.
Therapies: what and when?
“We know that every patient’s tumor is unique — but we also believe that there are common denominators, or growth pathways, that we can target with drugs,” Wellstein says.
“For example, breast cancer will likely be divided into 10 to 30 different kinds, and we will eventually work out which targeted therapies, given in the right sequence, offers the maximum therapy for each subtype,” Wellstein explains.
“That is where the future is moving, and we can make a very valuable contribution,” Wellstein says.
Disseminating a unique resource
Schlegel, who directs the Center for Cell Reprogramming, tapped Wellstein to take on the deputy director role to advise on research strategies, projects, and grants, and also to mentor faculty.
But Schlegel and Wellstein’s keen focus is to disseminate the technique, teach researchers from around the world how to use it and conduct original research using CRCs in prostate, breast, head and neck and other cancers.
The National Cancer Institute has already adopted the technique.
The technique has a wide range of applications beyond cancer, including regenerative medicine, and could prove significant to these fields.
Tool for understanding
GUMC researchers proved the CRCs’ potential in a 2012 article in the New England Journal of Medicine that showed how they used CRCs to find the right therapy for a 24 year-old man with rare tumors. Scientists screened potential treatments using the cells to identify which therapies were most effective against the tumor cells and least harmful to the normal cells.
While CRCs represent the apex of individualized cancer therapy, they can’t be used to tailor every cancer patient’s treatment, Wellstein says.
Instead, CRCs are a great tool to drive our understanding of cancer much more thoroughly, he says.
Doing so will allow investigators to figure out patterns that cancer takes, work out the best therapies for those molecular patterns, decode why some therapies work for some patients and not for others, and why some cancers escape treatment and others become resistant, Wellstein explains.
“Our job will be to figure out which drugs to use and in what order to wipe out the most virulent cells. But we will have the culprit in our laboratories, and so it is a matter of doing complex research.”
“This is all uncharted territory, but it can be done now,” Wellstein says. “And I find it fascinating — just fascinating.”
Georgetown University has an issued patent and pending patent applications on the technology described in this story. Schlegel and Liu are inventors on the intellectual property. In addition, Georgetown University has licensed the patent rights to a start-up company for commercialization. Schlegel serves as a consultant to this company, and Georgetown and Schlegel have ownership interest in the company.