Growth for the sake of growth, it is said, is the ideology of the cancer cell. That creed is firmly aligned with the human desire for long life. The longer we live, the easier it is for cancer—the universal name for a set of about 100 diseases—to turn our DNA against us.
Cancers are caused by the growth of abnormal cells, made malevolent by flaws in their DNA, their helical blueprint and control centre. DNA mutates either because it is inherited, or—much more likely—it is twisted out of shape by something in the environment, such as cigarette smoke, chewing tobacco or excess sunlight.
If their DNA is flawed, normal cells fix the problem or die. Cancer cells don’t want to die. They spread their flaws, as they grow faster and adapt better than normal cells, writes doctor and author Siddhartha Mukherjee in The Emperor of All Maladies, a biography of cancer. Since the body turns on itself, self-healing is difficult. For instance, in leukemia, white-blood cells, the body’s defenders, turn into traitorous killing machines, overwhelming their own army, the immune system. Cancer cells, Mukherjee points out, are “more perfect versions of ourselves”.
For decades, cures for cancers have focused on stopping the mutations of normal cells or killing mutated cells. Stopping mutations is incredibly complex because cancerous and normal cells share common genetic foundations. It does not help that cancers express themselves in varied fashion within individuals.
Solutions tend to focus on killing cancerous cells. There are two problems with this approach. First, as the debilitated state of many cancer survivors indicates, anti-cancer interventions, primarily chemotherapy, kill normal cells as well. Hair loss, nausea, vomiting and weight-loss are among the many effects of current anti-cancer treatments, quite a few akin to dropping a nuclear bomb to clear a city of garbage. Second, it is impossible to guarantee that all the cells will be eradicated; the survivors can easily restart invasion.
New therapies rooted in nanotechnology, the science of manipulating individual molecules, promise to detect and kill cancerous cells with minimal damage to healthy tissue. If these new approaches succeed, within two decades, some predict, cancer could become a chronic but manageable disease.
Some deploy gold, polymer or magnetic nanoparticles to ferry anti-cancer drugs to the heart of diseased cells. Others use nanoparticles to literally explode cancerous cells. A few adopt a Trojan-horse approach, infusing nanoparticles with special molecules that degrade the ability of cancer cells to defeat the immune system.
This last method has particular potential. Instead of drugs that supplant the body’s overwhelmed immune system, it uses immune response as a weapon.
It is a paradigm shift in the battle against cancer, a Gandhian approach of sorts. Martin Röcken says his group at the University Medical Centre Tübingen in Germany has been able to persuade tumour cells into a state of permanent dormancy without killing them. The results were published online this week in the journal Nature. “The immune system educates cancer cells to behave socially,” Röcken, told me. In other words, he adds, the cancer cells are prematurely aged, so they cannot grow.
How is this senescence—as the state of permanent dormancy is called—induced?
In animal models and in petri dishes, Röcken’s group used immune cells that produce interferon, a protein that is known to attack tumour cells, and tumour necrosis factor, (TNF), another protein that causes cell death.
Interferon and TNF attach themselves to receptors on cancer cells. In combination, their signals pulse through a complex of molecules that determines if a cell will grow or go dormant. “At this point,” says Röcken, “the two signals tell the cell: stop proliferation.”
This is a simplified explanation of what Röcken’s group does with cancer cells. There are, as with other cancer treatments, hurdles to overcome. The main obstacle is to get the right amount of interferon and TNF into cancerous regions. And as with other interventions, senescence research has not progressed to clinical, or human, trials.
Over the last four years, inducing senescence has become an area of particular interest. “We believe that a new frontier in cancer treatment will be to find ways to revert cancers to…dormant states by inducing tumor-cell senescence and vasculature normalcy or increasing the immune response to the tumour cells themselves,” says a 2008 paper in the Journal of Leukocyte Biology.
So, Röcken’s approach pushes the frontiers. It was only in 2005 that two papers in Nature first propounded the idea that cancer cells could be induced to senescence. Researchers have often used interferon and TNF in a variety of approaches to destroy cancerous cells and the blood cells that supply them. The Tübingen way, however, appears to show that surrounding tissues can escape unscathed.
As the era of finely targeted, personalized medicine approaches, the challenge will be to translate the promises of senescence into reality.
Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology. Comments are welcome at firstname.lastname@example.org. To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail