Candid Cancer: Victories are mounting in the 40-year war on cancer
Readers: This is part 2 of a report on the war on cancer. Part 1 is here.
Forty years into this war, technological advances have given scientists the tools they needed to explore deep inside our cells. They know that cancer begins with a single mishap within the nucleus, where 23 pairs of chromosomes essentially package two strands of DNA on which some 20,000 to 25,000 genes are scattered. They know that genes hold the instructions for regulating cells and that proteins carry out the instructions. And when cells receive the wrong instructions, they do things they're not supposed to do.
And how do cells get the wrong instructions? Normally, cell division begins in response to a signal received on the cell's surface which tells the tightly coiled DNA to unfold and copy itself. The signal is carried to the cell's nucleus by a series of proteins that make up signaling pathways. A mutation anywhere along the pathway can mean the wrong order is sent. Even when the right one arrives, our cellular copiers can make mistakes, leading to new genes that bark out the wrong orders. In the type of lymphoma that I had, for example, my cellular copier incorrectly crossed two genes, a mistake which generated a protein that told the new cells, "Don't die." Thus the proliferation of immortal cells began. Fortunately, our bodies have patrols that constantly neutralize most genetic mistakes, but get enough of them and cancer develops.
The good news? Thanks to technology that can see the behavior of cancer cells through the eyes of their genetic mutations, scientists are learning how to intercept the wrong cellular orders. And they're learning that dissimilar genetic mistakes can mean vastly different outcomes even in cancers that otherwise look the same. Take, for example, an aggressive type of lymphoma known as diffuse large B cell lymphoma (DLBCL), which is considered curable with a particular type of chemotherapy in about 60 percent of the cases. Scientists recently learned what's baffled them for years: the other 40 percent fare poorly because a specific genetic mutation in those cases resists chemotherapy. The challenge now is to develop a treatment that attacks the mutation.
Because scientists are at last unraveling the mechanism of cancer — and they're farther ahead in some types than others — a new era in treatment is dawning, one that will use drugs — some old, some new, some not yet discovered — that specifically target cellular flaws with laser-like precision. These targeted therapies began to emerge in the late 1990s. Essentially, they act like guided missiles, precisely homing in on the target while mostly sparing healthy cells, which means fewer side effects. Chemotherapy, on the other hand, is more like buckshot, hitting both malignant and healthy cells, or in my case, missing by a mile. (After chemo failed miserably, I was rescued in the nick of time by a targeted treatment known as radioimmunotherapy, pioneered by Dr. Mark Kaminski at U of M.)
So will chemotherapy ever meet its demise? Dr. Max Wicha, Director of the University of Michigan Comprehensive Cancer Center, predicts that other therapies — kinder, gentler, more effective therapies — will eventually replace it in about 10 years.
For some people, including me, with some types of cancer, targeted therapies have meant the difference between life and death. Dr. Wicha points to Herceptin, a drug used to treat breast cancer, as an example of success. Herceptin targets the HER-2 gene, found in about 20 percent of the women who have breast cancer, and now "about twice as many HER-2 positive women are cured than before we had Herceptin," he says. In order for Herceptin to work, women must have the HER-2 gene. It does nothing for those who don't, proof that targeting genetic abnormalities saves lives.
And there's Gleevec, a drug which targets a particular mutation that causes chronic myelogenous leukemia (CML). Gleevec tamed a disease that was always fatal into one that is managed like a chronic illness, much the same way that that diabetes or hypertension is managed: daily medication. Today, most people taking Gleevec survive and live normal lives.
So why have some targeted therapies been more successful than others? Dr. Wicha explains that cells have circuits, or pathways, in them, much like circuits in a transistor. He describes circuits as "kind of like a network, diagrammed like a spider's web." Using this analogy, genes send signals to each other along pathways within the spider's web. If one pathway is interrupted, the signal takes another. This means that the circuits have to be interrupted wherever signals travel, and it may take a combination of drugs to accomplish that mission.
Finding the right combination of drugs will also require analyzing the tumor of each individual patient for specific genetic abnormalities, and that in turn requires a huge amount of computing potential. Fortunately, Dr. Wicha tells me that technology is increasing at lightning speed, and programs are being developed that condense huge amounts of complicated data into forms that will tell physicians, "based on this data, you need to block X, Y and Z and use these three medicines to treat this particular patient. That's the key to the future," he says. And it's called personalized medicine, which is one of the main focuses of the North Campus Research Complex, the old Pfizer property of two million square feet that U of M recently purchased.
So the excitement in cancer therapy, Dr. Wicha tells me, is understanding the circuits. What's fascinating," he says, "is that some of the circuits that are wrong in one type of cancer are also wrong in others." Scientists have already discovered that CML and a rare cancer found in the gastrointestinal tract (GIST) share a genetic abnormality and that Gleevec turns off the proteins that cause the cancer cells to multiply in both.
It's not hard to see why specialists in cancer types are beginning to work across specialty lines even as researchers and pharmaceutical companies are developing new drugs that attack particular circuits — or why U of M and other major cancer centers are already categorizing cancers not just by where they are located in our bodies but also by their genetic mutations.
Clearly, a person's full genetic profile offers up a treasure trove of information, but what about the cost of genetic testing? When the human genome was first sequenced 11 years ago, the cost was about three billion dollars. "The cost to sequence now," says Dr. Wicha, "is about $7,000 and takes two weeks. In five years, it will cost $1,000 and take three days."
Will insurers pay for it? No one knows yet, but Dr. Wicha makes a strong case for cost effectiveness when he explains that many expensive treatments are being used now that don't always work because they don't target the individual patient's genetic abnormality. Figure out the right drugs in the first place, and the cost to treat would decrease considerably, not to mention human suffering.
I can attest to that. If treatment could have been tailored to my genetic flaw, I would have jumped for joy, and I'm sure my insurance company would have joined me. Instead, I spent several months in treatments that didn't work, assaulted by side effects, including some that required expensive hospitalizations, and all this cost the company $162,410. The treatment that did work took one week and cost $36,929. That's $4,344 per year for the eight and a half years that no money has been spent to re-treat, a bargain as cancer therapy goes.
And there's another frontier: cancer stem cells, which merits its own, soon-to-be written column. For now, it's not known that stem cells exist in all malignancies, but they are well established in CML, and U of M's Dr. Dale Bixby is trying to convert the disease from one that is chronic, managed by Gleevec, to one that is curable.
CML stem cells, he tells me, lie dormant in the bone marrow so long as patients stay on Gleevec, but stop the drug, they wake up, and cancer is back. And he adds, "Since Gleevec has only been around for 10 years, we don't absolutely know that the disease will lie quietly for 50 more years in a 30-year old person."
As the principal investigator of a trial which combines Gleevec and another drug, Dr. Bixby's goal is to completely eliminate those residual cells. If successful, says Dr. Wicha, "Patients will be able to go off Gleevec, and they'll be cured."
Not only is that great news for patients, but it will help ease the burden of health care costs. Dr. Bixby explains that while CML occurs in just under 5,000 people per year, the number of people living with it, thanks to Gleevec, is growing so rapidly that an estimated 150,000 people will be living with it in the U.S. alone by 2035, and that can spell high costs. "Our goal," says Dr. Bixby, "is to eliminate all remnants of the disease and get people off all drugs." That would be a win-win for everybody.
And speaking of health care, there's great debate about financial cost, but we're less comfortable talking about human cost. The fact is, people are dying — literally — for lack of access to care, and while everyone seems to want to win this war on cancer, we as a nation must decide if we're going to be satisfied with a win that carries some off the battlefield and leaves others to die. Would we provide fire protection for some and let the houses of others burn? Houses, at least, can be re-built.
Some of the battles in this war are, in fact, waged in the political arena, making it unrealistic to expect scientists to win it alone. And there's something else that needs figuring out: how to increase participation in clinical trials so that all the knowledge that scientists have gained in their labs are translated into gains for patients — faster.
In the meantime, we can all wage our own wars. It's estimated that lifestyle changes that reduce risk — quitting smoking, losing excess weight, exercising, consuming healthier foods, and screening for cancers for which screening is available — would slash the mortality rate by as much as 50 percent. Since the best cancer is no cancer, I say let's help scientists — indeed, ourselves — win this war.
So is victory on the horizon? Let's start with this fact: even if we do everything we can to minimize our risk, we're never going to get rid of cancer. Why? Cancer is a side effect of life because life requires the majestic process of cell renewal, and it's in this process that every cancer begins with a few mishaps. Unwelcomed, cancer cells then show up in various parts of our bodies with multiple variants and mutations, but they have one thing in common: they are masters of disguise with an uncanny ability to change their identity and to generate clones that are resistant to treatment. Block one of their paths and they deviously find another to continue their deadly march, even colonizing new territory in distant organs.
That's why fighting this war has been so hard. With multiple genetic variables, cancer must be fought — indeed, it is being fought — on multiple fronts. And since nobody wins a war on multiple fronts on the same day, it would be naÃ¯ve to think we will wake up one morning to a headline that reads, "Scientists Cure Cancer." Instead, victories will be won one battle at a time, just as they've been won all along.
And they are being won. Indeed, millions of people - including me - with all kinds of cancers are alive today — living our lives, loving our families — because campaigns have been waged and won, thanks to the explosion of knowledge and technology that has informed scientists how to turn hope into promise.
It's that very knowledge and technology, which is increasing exponentially, that will guide scientists to victories ahead, and victory will take on new meanings. Some cancers will be cured. Others will be beaten into lifelong remission and still others may be treated as lifelong chronic illnesses. However they happen, I'm painfully aware that new victories can't come quickly enough to help all who await them.
But at least now, victories are mounting faster than ever, and there is substantial reason, backed by science, to believe and expect that the number of lives saved will mount even faster. And lives saved — one child, one woman, one man at a time — is the true measure of victory.
Betsy de Parry is the author of Adventures In Cancer Land and the producer of Candid Cancer reports for the PBS show A Wider World which airs in this area on Tuesdays at 5:30 on WTVS. Find her on Facebook or email her.