A Researcher’s Perspective
Mapping the genome. Clinical trials. Personalized medicine. While these phrases might not mean much to patients, they are the lifeblood of oncology research. To David Spigel, MD, they are reasons for hope in the race to drive down cancer death rates.
A physician with Tennessee Oncology, Spigel directs lung cancer research at the Nashville-based Sarah Cannon Research Institute, a partnership of Tennessee Oncology and HCA. At Sarah Cannon, researchers are “interrogating tumors,” Spigel said, to discern cancer tumors’ differences and then develop unique ways to turn off their cell growth. Personalized medicine is here, and “it’s changed everything,” Spigel said.
Yet Spigel has an aversion to the term “personalized medicine” because it implies an across-the-board rethinking of medical care. “I can only speak for oncology, and that’s where I think most of the advances have been,” he said. “What personalized medicine is about right now is recognizing that a cancer that one individual has may be very different from what we thought that cancer would be like in other individuals.”
It hasn’t been that long ago that cancer treatment was a one-size-fits-all approach. “You have lung cancer? You fit into this box, and we give you this kind of treatment,” Spigel said. “What’s changed is a better understanding of what makes that lung cancer unique for that individual.” Therefore, researchers are now “subsetting” cancers, he explained, and the result is a more tailored approach to care.
Yet, Spigel stressed it’s more than just identifying a tumor. A physician can look at a lung tumor biopsy, for example, and call it a squamous cell carcinoma or an adenocarcinoma. And, yes, that identification is relevant in the patient’s care. “But what’s really been the breakthrough is an understanding of what are called genomic derangements,” he explained. “At the genetic level, what is it that drives or turns that cancer on, that makes those cells that were once normal behave abnormally? That’s the Holy Grail.”
At Sarah Cannon, much of the research and many of the clinical trials are pointed in that direction. Sarah Cannon is the largest clinical trial research institution in the country, offering patients opportunities to participate in trials that are available in communities across America and in the United Kingdom. More than 700 physicians are plugged into the network and coordinate trials not only in oncology, but also cardiology, gastroenterology and other therapeutic areas.
Spigel pointed to several Sarah Cannon cancer research initiatives that would fall into the category of Holy Grail searches. “The pace is so fast right now that it’s not hard to imagine that the landscape is going to be vastly different in just a few years than it is today,” he noted.
One project resulted in FDA approval last August of a new drug called Xalkori (crizotinib) for the treatment of late stage, non-small-cell lung cancer in patients who have the abnormal ALK (anaplastic lymphoma kinase) gene. That target isn’t common – it occurs in only 2 to 4 percent of lung cancer patients. “If you have that target, though, this pill is a remarkable drug,” Spigel said. “I would say this falls into the homerun category. This drug will do wonderful things for fighting that cancer.”
Another lung cancer trial at Sarah Cannon targets patients with an abnormality called MET overexpression. For some tumors, this MET “switch” is expressed in abundance, and in this randomized study, some patients are receiving an antibody via IV that specifically targets that overexpressed MET marker.
In an early drug development study, researchers are working to inhibit an enzyme called poly ADP ribose polymerase (PARP). “Cells repair themselves, and cancer cells are no different,” Spigel said. “They have figured out how to repair themselves, and the PARP protein is one of the ways they do this.” Thus, researcher are developing PARP inhibitors, which have the potential to be particularly effective against ovarian and some breast cancers.
Another Sarah Cannon research project regarding breast cancer targets the PI3 kinase pathway, which scientists believe might be a reason why some cancer cells become resistant to chemotherapy. “We can target that with a drug that hopefully will shut that pathway down, and we have many PI3 kinase inhibitors in development,” Spigel said.
“Right now, the future is so bright. There’s so much reason to be hopeful about our better understanding of cancer and how to design therapies to be more effective in those particular cancers,” Spigel concluded. “To be part of that, not only as a doctor who takes care of patients but also from the research side to design trials and try to help find new therapies, is really exciting.”