"I was wrong."
Words not often heard from a senior scientist, now spoken by William Blackstock Jr., MD, chair of radiation oncology at the Wake Forest School of Medicine and director of the clinical research program at the Wake Forest Baptist Medical Center Comprehensive Cancer Center.
Blackstock is a visionary, but even visionaries can be wrong. He was initially skeptical about the value of cancer immunotherapy research and was pleasantly surprised when immunotherapy thoroughly changed the landscape of cancer treatment. “The return on investment has been tremendous, and in the last five years, it’s exploded,” he observes.
As a leading member of Wake Forest Baptist’s cancer biology research team, Blackstock is among a host of investigators working to move cancer research forward, from cell culture to experimental animal models to human patients.
Where We Stand, Where We’re Going
Blackstock laughs easily and heartily, and often at himself, but when it comes to what’s next in cancer biology, he speaks profoundly from his wellspring of decades of experience in the field.
His opinions hold substantial weight—he’s a nationally recognized expert in the radiotherapeutic management of cancers, with a primary focus on gastrointestinal cancer treatment. With extensive experience leading Phase 1 and Phase 2 clinical trials involving novel radiation cancer treatment approaches, he predicts that major improvements in cancer treatments are right around the corner.
For example, he foresees that the next frontier in immunotherapy is to develop “cocktails” of multiple immunotherapeutic drugs, akin to the approach that ultimately was so effective in HIV/AIDS treatments.
“We are really pushing cancer as more of a chronic disease,” he says. “Where once we would give a patient a survival estimate in months, now it’s measured in years. I would love to say it’s 10 or 20 years. It’s not that yet, but it’s years, so that you go about your business, you go to work and do your job, you take your cocktail, and live with a good quality of life.”
Blackstock has been chair of radiation oncology at Wake Forest Baptist since 2008. His active life at the lab bench is behind him now—today he manages the institution’s team of researchers and clinicians delivering state-of-the-art radiological therapies and bringing about tomorrow’s innovations in the field. With a medical degree from the East Carolina University Brody School of Medicine, he completed his residency and fellowship training in radiation oncology at the University of North Carolina School of Medicine. In 1996, he traded in his Carolina blue for black and gold at Wake Forest, where he has continued to grow as a clinician and researcher.
As Blackstock reflects on the developments in radiation oncology over the last decade or two, he is enthusiastic about the significant advances seen in the field. He is especially excited about improvements in accuracy and the ability to take tumor motion into account.
“Back when I was in training, you really couldn’t track tumors, because with lung cancer, when you breathed, the tumor moved, and we had no ability to compensate for that motion,” he explains. “Now, we have the ability to track tumors in real time.”
When he was a resident fellow, that capability was only a dream.
He sees the integration of imaging as another major step forward.
“The chairman before me actually presciently installed an MRI scanner, a PET CT scanner and a CT scanner. Most radiation oncology practices only have one, usually a CT scanner to do the radiation planning. We integrate all of those different modalities into what we do in terms of radiation planning, and it is much better now in terms of side effects—no question about it.”
Cancer biology is progressing rapidly in many other areas as well.
Blackstock believes that major advances in precision medicine and biomarker-directed therapy will also contribute to extended cancer survival in the coming years. Today, breakthroughs in those areas are improving medical oncology, but for radiation oncology, they are just starting.
“But rest assured, they are coming, as biomarkers predictive of response to radiation will be integrated into therapeutic strategies, along with treatments with newer particles like protons and carbon,” Blackstock says.
Another leap forward will be the ability to use radiation to treat cancers that have metastasized beyond the primary tumor site. It’s called oligometastatic radiation therapy. Blackstock thinks it could be a game-changer for radiation oncology.
“We did our first trial that finished about a year ago, and wow, the data!” he says. “There are people who are now out years from treatment who I never would have anticipated.”
He proudly foresees that Wake Forest Baptist will play a central role in development of the technology.
“Our findings are going to contribute to what limited data there is, and there is going to be a big push for oligometastatic radiation in the future,” he says.
For Blackstock, the revolution in cancer biology is more than just publications and professional recognition—it’s deeply personal, touching his own circle of associates and family.
A close coworker who has non-small cell lung cancer “can now look forward to years of survival, not just months,” Blackstock explains. And a family member “was diagnosed recently with advanced lung cancer. She still goes to work every day. We’re going to celebrate her year from diagnosis tomorrow, and she looks better than me, which is not hard to do!”
He chuckles a little. He says her path would have been much different five or 10 years ago. Today, she is benefiting from immunotherapy-based strategies—the very ideas Blackstock had previously doubted.
Building a Team of Top-Notch Researchers
Blackstock and his colleagues are devoted to the concept of translation, although he recognizes that conducting truly translational work is quite challenging.
He notes, “We are really focused on translation, and the institution [Wake Forest Baptist] is committed to competing for the top scientists in the country.”
Those efforts are paying off—bringing Blackstock much joy at this stage of his career.
“That’s when you really do have fun, because when we bring young people in, those young people do incredible things.”
Wake Forest Baptist researchers, both budding faculty and more established members, encompass interdisciplinary efforts from basic science through clinical trials to address some of the biggest hurdles in cancer biology research.
While Blackstock is currently immersed in clinical care and radiation research, his work complements a host of investigators at Wake Forest Baptist—each at different stages of the research process leading to human application.
Singh: Fighting cancer at the nano scale
Ravi Singh, PhD, assistant professor of Cancer Biology, is one of a small community of researchers around the world exploring the biomedical applications of nanotechnology. He is working to develop nanomaterials for clinical use.
At the tiny nano scale, materials have extraordinary properties that don’t exist at the normal scale. Within the realm of cancer therapy, those properties can be leveraged to take advantage of the unique capabilities they offer to enhance cancer diagnosis and therapy. Singh is a leader in this exciting, emerging field.
His research program is divided primarily into two arms: one based on metallic nanomaterials, the other based on carbon nanomaterials, both of which offer unique properties of great anti-cancer value.
In metallic nanomaterials, Singh and his group have been working with silver nanoparticles.
“Our work is based on a discovery made about eight years ago that we could use silver nanoparticles to selectively sensitize a subset of aggressive breast cancers, collectively known as triple-negative breast cancers, which are often associated with poor prognosis because they cannot be targeted with current therapeutics,” he explains. “We can selectively sensitize those cells to ionizing radiation by treating them with silver nanoparticles prior to the administration of the radiation.”
“Subsequently, we’ve discovered that the nanoparticles themselves, even in the absence of ionizing radiation, are highly cytotoxic to these triple-negative breast cancers, but do not harm normal breast or other non-cancerous cells,” Singh notes. “Most importantly, we have identified shared biomarkers that predict response to silver nanoparticles across multiple cancer types including lung, ovarian, prostate and colorectal cancers, in addition to breast cancer.” This forms the basis for using genetic screening to identify patients with tumors that are likely to respond to treatment using silver nanoparticles.
The second line of Singh’s research is focused on carbon nanotubes—specifically, the ability of carbon nanotubes to convert near-infrared radiation into heat. It turns out that treatment with carbon nanotubes is very effective at killing cancer stem cells, which tend to be quite resistant to current therapies. The cancer stem cell tumor subpopulation is believed to be responsible for disease resistance, recurrence and eventually patient death, so the ability to target the stem cell could make treatments much more effective and prevent recurrence.
Although his work is currently at the preclinical level, Singh’s goal is to develop the nanomaterials for clinical translation.
“At this point, we need to refine the materials precisely and begin the process of developing investigational new drug applications in anticipation of future clinical trials,” Singh adds.
There are a number of nanomaterials already in clinical use, so the future would appear to be bright for applications in cancer.
“The next stage in the evolution of cancer nanotechnology is not use of nanotechnology in patients—that is already occurring. What we are finding is that nanotechnology may have a role in the emerging precision medicine paradigm. Our focus now is answering the question of whether it is possible to increase treatment efficacy and reduce toxicity by matching specific nanomaterials with a specific patient’s type of cancer,” Singh says.
Cline: Treating animals with cancer while testing novel therapies
J. Mark Cline, DVM, PhD, professor of Pathology/Comparative Medicine, is a veterinary pathologist and leader of the Primate Cancer Initiative. He studies cancer risk, prevention and treatment in nonhuman primates.
Monkeys have much to reveal about cancer in humans.
“We noticed at least a decade ago that monkeys have more cancers than are generally realized, and that they have a pretty high incidence of breast, cervical and colon cancers, which are prevalent in people too,” Cline says. “And so we thought, is there an opportunity here to explore novel ways to treat these cancers in monkeys because they’re so molecularly similar to us?”
That was the genesis of the Primate Cancer Initiative, the only program of its kind. It accepts nonhuman primates from facilities around the world—animals found to have naturally occurring cancer that would otherwise have been euthanized. If accepted into the initiative, the animals are brought to Wake Forest Baptist, where their cancers are treated through pilot studies for novel therapies.
“For animals that come here and have been treated, we often send photos back to the donor to say, here’s the animal, and they’re doing well,” Cline notes.
During treatment, the researchers use PET imaging to look at whether the drug goes to the cancer. They conduct biopsies before and after dosing to track response and see if the drug has had the anticipated effect. They also check for off-target effects, which can occur months or years later in human immunotherapy patients.
As the cohorts are small, the primates in Cline’s program are ideally suited for these pilot studies.
“If a study sponsor has designed a highly specific, customized molecule that is supposed to go only to the tumor, we can test that in a species that is 97 percent genetically identical to people,” Cline observes. “The benefit for sponsors is proof of concept studies of tumor targeting.”
In addition to the Initiative, Cline also manages an NIH-supported project called the Radiation Survivor Core, an offshoot of a radiation countermeasures consortium that arose initially from the events of 9/11. That program was oriented toward mitigating radiation injury. Cline’s team takes in nonhuman primates that have had radiation exposure and studies the long-term health outcomes of the exposure. Today, the program operates in collaboration with Duke University, NIH and the Department of Defense.
Taming Cancer with Science
Blackstock knows there is something special going on in cancer biology research at Wake Forest Baptist.
“I know that the institution feels that cancer research is one of the main things it wants to emphasize,” he says. “We’re one of the flagship offerings to the national community. The resources made available by the Medical Center have been, to me, incredible. They’ve given us the opportunity to recruit people who are going to be the best in their fields, who will know that their programs will be sustained.”
Across the institution there are more like Singh and Cline, each contributing in a tangible way to the new paradigm predicted by Blackstock—a day when cancer is understood to be a chronic condition, with long-term survival all but assured.
Investment in basic research and subsequent commitment to translation will undoubtedly bring that day to pass. The only question is how long it will take to arrive in full force. Visionary scientists at Wake Forest Baptist and around the world are working to bring the dawn of that new day closer.
Blackstock may have underestimated immunotherapies, but he is certainly right about the long-term outlook for cancer biology. Hope is on the horizon, and the future is bright.