What If Cancer Simply Can’t Be Cured?
WHY YOU SHOULD CARE
Because cancer’s deep, ancient roots might mean it’s here to stay.
Since Richard Nixon declared War on Cancer in 1971, the National Cancer Institute has poured some $90 billion into research and treatments. Yet a cure remains elusive. Experts blame everything from a flawed emphasis on treatment over prevention to Big Pharma betting on blockbuster treatments that cost billions to develop.
Cancer…will probably never be completely eradicated.
But a new study raises a sobering possibility: that cancer may simply be here to stay. Researchers at Kiel University, the Catholic University of Croatia and other institutions discovered that hydra — tiny, coral-like polyps that emerged hundreds of millions of years ago — form tumors similar to those found in humans. Which suggests that our cells’ ability to develop cancer is “an intrinsic property” that’s evolved at least since then — way, way, way before we rallied our forces to try to tackle it, said Thomas Bosch, an evolutionary biologist at Kiel University who led the study, published in Nature Communications in June 2014.
To get ahead of cancer, he said, “you have to interfere with fundamental pathways. It’s a web of interactions,” he said, adding that it’s very difficult to do. That’s why we’ll most likely “never get rid of” our potential to develop cancer.” Cancer results from DNA mutations that throw a wrench into the molecular circuits that regulate the cell cycle. Unregulated, cancer cells multiply uncontrollably. They also evade a process known as apoptosis, in which cells with genetic mistakes essentially commit suicide.
Bosch and his colleagues have investigated hydra stem cells and tissue regeneration for years. In an earlier study, they showed that these pulsating polyps carry genes that can cause cancer in humans. But, they wondered, did those genes also trigger tumor growth?
Sure enough, they discovered tumor-ridden polyps from two hydra species. Oddly, the tumors ravaged only female polyps. They bred them for five years, generating several clones of each.
Cancer…has ‘deep evolutionary roots,’ adapting to its host’s defenses with an arsenal of different strategies.
To unravel the tumor-causing mechanisms, the researchers observed cell division in hydra with and without tumors. They saw that stem cells programmed to turn into female sex cells, or eggs, divided uncontrollably. They accumulated in vast qualities without being naturally culled through apoptosis — resembling ovarian cancer in women. They then sequenced the tumorous hydra’s DNA and discovered a gene that halts apoptosis and whose activity runs amok in tumor tissue. Turns out a similar gene hijacks apoptosis in humans and also spurs unbridled cell proliferation.
So we know that tumors can grow in hydra, but are hydra tumors invasive the way they are in humans? To find out, the researchers transplanted tumors into healthy polyps. Indeed, cells from tumors transplanted in the midsections of healthy polyps migrated all the way to both ends of their bodies.
All this means that cancer genes, plus the mechanisms that allow tumor cells to evade death and invade healthy tissue, “have deep evolutionary roots,” the researchers wrote. “Any crucial cell in your body can at any point make a mistake,” and there’s no way to prevent it, Bosch said. “You carry a time bomb in your body when you’re born. It can explode early in life, or middle age or later.”
But, Bosch adds, “that doesn’t mean that, with a patient who develops cancer, there’s nothing you can do.” While our cells will probably always have the ability to make mistakes that trigger cancer, Bosch believes “medical technology will allow us at early time points … at least in some cases, to successfully treat and clean a patient completely and forever of troublemaking cells.”
One strategy might be to unleash the immune system against these cells. Advanced melanoma patients treated with Yervoy, a drug that does just that, combined with a chemotherapy drug called dacarbazine, were twice as likely to survive five years as those who underwent only dacarbazine treatment in a phase 3 trial described in the Journal of Clinical Oncology in April. Meanwhile, an early-stage clinical trial found that up to 39 percent of advanced non-small cell lung cancer patients responded to a combination of Yervoy and a similar drug, Opdivo.
Next up, Bosch and his lab are working to understand how tumor cells avoid apoptosis, testing the hypothesis that, unlike healthy cells, tumor cells don’t respond to chemical signals that tell them to undergo apoptosis. Another line of research involves understanding the role of the bacterial ecosystem, or microbiome, on the surface of tumor cells. Scientists have known for years that the microbiome of tumor cells differs from those of healthy cells in humans. Bosch’s group also see these differences in hydra. Now want to determine whether the disturbed molecular processes in tumor cells changes the microbiome or whether an abnormal microbiome alters those molecular processes – triggering cancer.
Indeed, basic research on the evolution of cancer’s arsenal remains crucial. “Knowing your enemy from its origins is the best way to fight it and win many battles,” Bosch said. Our goal, then, if we can’t slay the beast, is to learn enough about it that we render it harmless.