“The question was whether having an oncogene also meant that you would be resistant to radiation, which would certainly impede the effectiveness of cancer treatment.”

- Adam Garden, M.D.

Funding Radiology’s Future

RSNA Research Fellow Tests Radiation Resistance Despite Skepticism

Call it a case of bad timing. Just as Adam Garden, M.D., submitted his research proposal to examine the role of activated oncogene expression in radiation response, skeptics began to question the validity of previous research findings.

“It was like cold fusion at the time,” said Dr. Garden of the early research into radiation response. “Initially, everyone thought cold fusion was great until it got off the ground, then people began to think it might not be so legitimate.”

Dr. Garden, now a professor of radiation oncology, section chief of head and neck radiation oncology and associate medical director of the Head and Neck Center at the University of Texas M.D. Anderson Cancer Center, began his RSNA Research Fellowship more than 15 years ago while working as an assistant professor and assistant radiotherapist at the highly acclaimed Houston cancer treatment center.
 
As he launched his project, Dr. Garden said, people were starting to recognize the oncogene and suspicion was surfacing suggesting that the cancer-inducing gene might also influence cellular radiation response.

 “The question was whether having an oncogene also meant that you would be resistant to radiation, which would certainly impede the effectiveness of cancer treatment,” said Dr. Garden.

Building on previous research demonstrating the suspected radiation resistance, Dr. Garden and his team first sought to identify a cell line that would show whether or not said resistance was a reality. It was this element that proved to be their biggest struggle—just as their research was getting under way.

Skeptics of radiation resistance, Dr. Garden said, questioned whether the resistance originally discovered might have been a function of mutations within the cell lines developed for the research, rather than from the oncogenes themselves.

While Dr. Garden and his team agreed the original study had some flaws, they felt there was still ample evidence to suggest that oncogene expression does influence radiation response.

Dr. Garden went on to confirm this hypothesis by developing an “on-off switch” of sorts. He first identified a cell line that allowed him to link an oncogene to zinc, then manipulated the zinc to turn the oncogene on and off. He was able to demonstrate there was more radiation resistance when the oncogene was “on” than when it was “off.”

“Adam did indeed confirm a role for the Ras oncogene, however the effect was small,” said Raymond Meyn, Ph.D., professor and interim chair of the Department of Experimental Radiation Oncology at M.D. Anderson, who oversaw Dr. Garden’s research.

“We now understand that the response was not larger because human cancers have defects in multiple genes and the interactions of these defects impact radiation response in a complex manner,” Dr. Meyn said. “So now, 15 years later, we are preparing to take advantage of Adam’s finding by using molecular targeting agents to inhibit the Ras pathway and thereby enhancing tumor response to radiation.”

Dr. Garden takes pride in the fact that his was one of the early works that lent validity to molecular targeted therapy—a concept with a great deal of potential that he feels is still in its infancy.

“Molecular targeting of cancer is a highly promising therapeutic strategy, especially when combined with radiation,” said Dr. Meyn. “However, based on Adam’s original findings and the work from many other laboratories, it’s clear that we may have to target several of the molecular pathways that are defective in a tumor to be successful with this approach. This will ultimately require detailed knowledge of the molecular defects specific to each individual patient’s disease.”

Dr. Garden graduated with honors from Johns Hopkins University and received his medical degree from SUNY Health Sciences Center in Brooklyn. He completed his internship and residency at Staten Island Hospital in New York before joining M.D. Anderson in 1986. He said that his 1989-1990 RSNA Research Fellowship experience strengthened his resolve to pursue research. 

“The RSNA program introduced me to a more rigorous academic environment than I had seen previously and validated my desire to stay in a research setting,” said Dr. Garden. “So after my fellowship, I stayed on as clinical faculty at M.D. Anderson and followed an academic clinical track where, in addition to treating patients, I have been involved in multiple research efforts looking at outcomes and ways to improve treatment for patients with head and neck cancer.”

For more information on RSNA Research & Education Foundation grants and giving programs, visit RSNA.org/foundation.

Former RSNA Scholar Receives ACS Grant

Reed Omary, M.D., a former RSNA Research & Education Foundation Bracco Diagnostics Research Scholar, has received a $100,000 grant from the American Cancer Society, Illinois Division. Dr. Omary, of Northwestern University School of Medicine in Chicago, received the grant for a study titled “Functional MRI Assessment of Hepatic Artery Embolization.”

Andy Larson, M.D., and Riad Salem, M.D., are co-investigators on the study. Using a VX2 rabbit model of hepatocellular carcinoma, the study aims to measure the ability of an improved MR imaging technique to differentiate necrotic from viable tissue in liver tumors and to compare functional vs. anatomic MR assessment of tumor response following transcatheter arterial embolization.

Dr. Omary said he and his colleagues hope to gather important preliminary data for an upcoming National Institutes of Health R01 grant submission. He added that radiologists should be aware that the American Cancer Society can serve as an important avenue for potential grant funding.