From Medical Daily
Though spring arrived last week, morning temperatures still are hovering around freezing, while inside Columbia University’s Low Library Rotunda, high arched windows shine with pale sunlight. An assembled crowd listens to a panel of scientists who sit beneath a stone balcony occupied by four marble statues of historical greats, Sophocles among them — ancient men draped in ancient robes yet somehow resembling contemporary cancer patients shuffling through a hospital corridor toward a CT scan. Though many strongly-held opinions echo in this dramatic rotunda, it is the voice of Dr. Andrew L. Kung that resounds with the greatest hope as he speaks of a new narrative of cancer.
“Instead of talking about brief remissions, our measure of success is, really, cure. ‘Cure’ meaning forever,” said Kung, professor of pediatrics at Columbia University Medical Center. “We cure 80 percent of all kids that come in with cancer.” This doctor who is also chief of pediatric oncology at NY-Presbyterian/Morgan Stanley Children’s Hospital underlines his point: “That success, I think, is a strong counter-narrative to those who would argue that we are losing the war against cancer.”
Kung is speaking within the context of a media briefing for the TV program “Cancer: The Emperor of All Maladies.” This three-part, six-hour documentary is based on the Pulitzer Prize-winning book by Dr. Siddhartha Mukherjee, oncologist and assistant professor of medicine at Columbia, and it will air on PBS for three nights in succession: Monday, March 30, Tuesday, March 31, and Wednesday, April 1. This TV program chronicles the history of cancer research while celebrating the moment when everything suddenly changed.
Unified Theory of Cancer
By the mid-1970s scientists had made little progress toward solving a painful mystery: What causes cancer? Those working in the field saw how viruses in some cases could instigate the disease, but they observed how chemicals sometimes ignited cancer, too. Shortly, researchers stumbled upon one more independent cause, when they established a relationship between inherited genes and the disease.
Viruses, chemicals, genes: Though none of these three theories were wrong, all were insufficient. Mukherjee evoked the Indian story about three blind men and an elephant to explain this period in medical history. Though separate scientists had described, perfectly, different aspects of cancer, no one scientists was able to step back and see the entire beast. No one could supply a unifying theory… until 1976.
In that year, collaborating scientists J. Michael Bishop and Harold E. Varmus identified an existing gene that regulated cellular growth yet when it was disrupted — by a virus, say, or chemicals — this so-called oncogene acted as the trigger that unleashed cancer.
“We have not slain our enemy, the cancer cell,” said Varmus, who is now director of the National Cancer Institute, when accepting his Nobel prize two decades after his discovery. “We have only seen our monster more clearly and described his scales and fangs in new ways — ways that reveal a cancer cell to be a distorted version of our normal selves.”
That, as they say, was then, and this is now. Focusing on pediatric oncology, Kung’s telling of the “modern story” of his branch of medicine begins with the hallmark publication in 1948 of Dr. Sidney Farber’s research. Farber’s paper showed the very first chemotherapy agent briefly inducing a reduction in leukemia for children with acute lymphoblastic leukemia. Over 65 years, outcomes have steadily improved and today, “of all the kids who present to us with acute lymphoblastic leukemia, 90 percent of kids are now cured of their disease,” Kung said.
This heart-warming success is built on research that showed how cancer is not one disease but hundreds; how cancer can be cured by combining different drugs; and how treatments must be tailored to each patient’s individual disease. These three precepts underlie the contemporary concept of precision medicine, says Kung, however it’s not over yet, some concerns still remain.
“We went through an era where we couldn’t really worry much about what happened down the road because we were so intent on making sure that we cured the patients,” Kung toldMedical Daily. Now the delayed effects of treatment are of equal importance when treating kids. “And it’s not just secondary cancers, it’s fertility, it’s neurocognitive effects, it’s growth, it’s a plethora of things we have to be mindful of as we set about curing the cancer,” Kung toldMedical Daily.
Each cure, he explains, begins with sequencing every gene in a patient’s body in addition to every gene in their cancer. That’s 25,000 genes, Kung says. Sequencing, like the bread crumb trail left behind by Hansel and Gretel, can lead the way to the proper drug for about 30 percent of his patients, but “that other 70 percent isn’t going to be informed by the genes,” Kung tellsMedical Daily, “It’s going to be informed by the RNA and the protein expressed by the genes.”Epigenetics, in other words, will edify the next wave of precision medicine.
Not satisfied with an 80 percent cure rate, Kung is chipping away at the remaining 20 percent through research as he continues to learn how to decrease toxicity in the drug regimens for kids. “Our ability now to not have to focus on individual genes, individual proteins, but actually being able to look comprehensively at everything really is I think what’s transformative about the current science,” Kung told Medical Daily. “That’s what we’re all excited about.”
By Susan Scutti for medicaldaily.com