PBS "Emperor" Broadcast Stokes a Discussion on Cancer Research's Future
By Walter Alexander
As a medical discipline oncology is rooted in deeply personal experiences, which were underscored by a panel hosted by Columbia University as a prelude to the recently aired PBS three-part series, “Cancer: The Emperor of All Maladies.” The series was based on the book of the same title by Siddhartha Mukherjee, MD, PhD, who participated in the panel along with the series’ executive producer Ken Burns, and its director Barak Goodman, global news anchor for Yahoo! News Katie Couric, Columbia physicians and professors Stephen Emerson, MD, PhD, Cory Abate-Shen, PhD, Gary Schwartz, MD, Kenneth Forde, MD and Thomas Maniatis, PhD, NY-Presbyterian pediatric oncologist Andrew Kung, MD, Johns Hopkins’ William Nelson, MD, PhD, and UCLA’s Dennis Slamon, MD, PhD.
Ms. Couric, who lost her husband to colon cancer and her sister to pancreatic cancer made the point that “today more than ever the story of cancer is a story of hope.” A devoted advocate for patients with cancer and an activist, Ms. Couric cofounded the National Colorectal Cancer Research Alliance and the Stand Up to Cancer initiative. She’s used her own colonoscopy and mammograms as subjects of major network television programs.
Ken Burns told the audience of losing his mother to breast cancer when he was 11 years old, and of the immediate cancer histories among people associated with the series, including film producer Laura Ziskin (d. 2011) and Ed Herman, who succumbed to brain cancer just days after completing the documentary’s narration. “Our film is bracketed by death from this insidious disease,” he said.
Mr. Burns had been convinced (or rather “ordered”) by Sharon Rockefeller (who herself had emerged from life-threatening cancer) to take on this project despite an overcrowded lists of commitments. He said that after reading Dr. Mukherjee’s book, and “…understanding how my own mother’s death had formed me and who I am now—telling histories, waking the dead, trying to have conversations with people no longer here—it became obvious that somehow I had to do this.”
The challenge, he said, in telling this “most important detective story ever” and of presenting complex science to a lay audience, was finding ways of understanding and illustrating the science that would transcend the usual narratives. “But also, it had to be anchored in concrete experiences,” and could not leave out the patient. “We felt obligated to anchor this with stories of real human beings like me who suffer, who relate, who lose, who gain, who are cured, and who die from this disease.”
In four years of imbedded journalism at cancer treatment centers, “we had the privilege to witness that unique interaction between caregivers and the patients and their families,” and to assemble a “mongrel collection of history and science and intimate stories that we are extremely excited to share with you.” Regarding the extensive segments on the history, present and future of oncology research, he added, “we have the finest set of talking heads we’ve ever had in any film.”
Describing challenges such as those of conducting cancer research and clinical trials, and working around resistance to drugs, Dr. Mukherjee said, “We have met cancer point for point for point, and we will continue…but that requires participation from everyone. It is your disease as much as my disease. It will affect my children as much as it will affect your children—we are all equally a part of this story.”
Dr. Mukherjee further lamented the weakening of research support, which he described as anemic despite dramatic recent advances. “We are performing this task with progressively depleted troops. The national will, I think, has gone out from under us.” Research funding, he said, is 20% lower than it was before the recent advances in genomic understanding of the causes of cancer and the subsequent innovative therapies arising out of that understanding. Not supporting “truly disruptive, transformative technologies,” is indicative of “an era of madness,” he commented.
The successes of cancer research, according to Dr. Kung, chief of pediatric oncology at New York-Presbyterian/Columbia University Medical Center, are clearly manifest in the progress in treatment of many childhood cancers—specifically, in acute lymphoblastic leukemia (ALL) since Sidney Farber first described the brief chemotherapy-induced remission in 1948. “The narrative is now quite different. Where instead of talking about brief remissions, the measure of success is now cure—with ‘cure’ meaning forever.”
The contemporary success rate of 80% for all pediatric cancers, and 90% for ALL Dr. Kung said, “Is a strong counter-narrative to those who argue that we are losing the war against cancer.”
Years of cancer research have taught that cancer is not one disease, but hundreds of different diseases. “One size doesn’t fit all; individuals who present to us with cancer must be treated in a way that is tailored to their individual disease,” he said. In Dr. Kung’s clinical practice, all patients have every gene (25,000) sequenced, along with every gene in the tumor. “With precision medicine, we are chipping away at the 20% who are not cured, and—we want to get to 100%.” Advances, he said, will occur across all of oncology.
William G. Nelson, MD, Johns Hopkins University, noted that among men diagnosed with prostate cancer, 97% of them are still alive five years later and the most likely cause of their ultimate deaths will be not prostate cancer, but heart attacks. Ironically, he said, one of the most common treatments for prostate cancer increases heart attack risk. “[This] may not be the perfect way to use that treatment,” he commented.
New targeted therapies are a means to treat “what’s broken in a cell that allowed it to convert from a normal cell to a malignant cell—and therefore hit its Achilles’ heel,” said Dennis Slamon, MD, UCLA Jonsson Comprehensive Cancer Center. Acknowledging that the targeted therapies sound “incredibly exciting,” Ms. Couric inquired about their toxicities, side effects, and propensity to stimulate secondary cancers.
“I used to call chemotherapy a ‘scorched body’ approach—where you kill everything and hope the normal cells will grow back…where are we with these more elegant ‘heat-seeking missiles?’” she asked.
Dr. Slamon responded, “In theory, if you’ve done it right, normal cells don’t have that Achilles heel, so you should have a therapy that is (a) more effective, and (b) less toxic.” While there is always some toxicity with any drug, he said that for many of the targeted therapies, side effects are minimal compared with what has been typical with cancer therapies.
Dr. Slamon also noted that taking a drug such as Herceptin and linking to a chemotherapeutic agent as opposed to administering it side-by-side with chemotherapy has eliminated the hair loss, nausea, and vomiting that patients typically experienced when the antibody was given alongside chemotherapy. “There’s a lot of excitement over the fact that we are going to be able not only to dial up efficacy, but also dial down the safety concerns and toxicities. That’s really the ideal of an ideally targeted therapy.”
The issues of survivorship and toxicity are particularly poignant in pediatric cancer where the still-developing patient is exposed to powerful therapies. “We reached a level of success, and with the evolution and revolution of the precision medicine era,” Dr. Kung said, “I think we can do much better in terms of outcomes and decreasing toxicities for those whom we cure…Precision medicine is also about knowing what drugs not to use…guiding us on where to go and where not to go.”
Dr. Cory Abate-Shen, professor of urology and pathology echoed that view. “We are at the point of being able to identify many cancers at a very early stage—in colon, prostate, breast, and now in lung –and presumably many other cancers along the way. And so now we have a different problem – whom do we treat and whom do we not treat?”
Traveling the road toward answering these and other essential questions, the panel agreed, calls for greater funding. Ms. Couric said at the outset, “Sadly the researchers on the front lines too often lack the funding they sorely need to make meaningful progress.” She portrayed the founding of Stand Up to Cancer by a group of prominent women in the entertainment industry as a reflection of the observation that “hell hath no fury like nine type-A women frustrated by the seemingly slow pace of progress in cancer research.”
Stand Up to Cancer, after 7 years and 4 telethons, has funded 13 research “Dream Teams,” 26 individual investigators with “outside the box” ideas, and more than 800 scientists collaborating at 115 institutions around the world. More than 120 Stand Up to Cancer-funded clinical trials have enrolled over 5,200 patients. “We are pressing the gas pedal on cancer research, and we are not going to stop until our scientists are able to produce effective, important and meaningful new therapies,” said Ms. Couric.
Ken Burns commented, “If cancer is indeed the ‘emperor of all maladies,’ then we are all its subjects and are obligated to become part of a resistance movement.”