The cover story in this weeks Time magazine is a good analysis of what’s required to fight this deadly disease and does not hold back when they suggest that more collaboration and a whole lot more money. For pharmaceutical companies, it means restructuring the way experimental drugs are allocated and clinical trials are conducted. “This disease is much more complex than we have been treating it,” says MIT’s Phillip Sharp. “And the complexity is stunning.”
Cancer is not just one disease; it’s hundreds, potentially thousands. And not all cancers are caused by just one agent–a virus or bacterium that can be flushed and crushed. Cancer is an intricate and potentially lethal collaboration of genes gone awry, of growth inhibitors gone missing, of hormones and epigenomes changing and rogue cells breaking free. It works as one great armed force, attacking by the equivalent of air and land and sea and stealth, and we think we’re going to take it out with what? A lab-coated sniper?
Cancer research–indeed, most medical research–is typically about the narrowly focused investigator beavering away, one small grant at a time. But advances in genetic profiling of malignancies and the mutations that cause them are telling scientists and physicians they must stop working in these kinds of silos, treating lung or breast or colon or prostate cancer as distinct diseases. “You no longer do science and medicine differently,” says Dr. Lynda Chin, director of the Institute for Applied Cancer Science at MD Anderson Cancer Center. “It brings science and medicine together.” Common genetic mutations, like one called p53 that controls cell death, are showing up across a whole swath of cancers. A mutation called BRCA1 is common in women’s cancers such as breast and ovarian, yet the research and clinical work in those two diseases has largely been separate.
The only way to take advantage of the dazzling scientific and technological advances that have taken place in just the past three years–advances in bioengineering, nanotechnology, drug compounds and data gathering, including protein data, splicing data and mutation data, all of which is being hoisted into view by ever cheaper computational muscle. Sequencing the first human genome took more than a decade and $2.7 billion. Today sequencing can be done for a few thousand bucks in a few hours. That progress has led to similar pharmaceutical leaps. Hundreds of drug agents are in development for therapies targeting the genetic mutations that have thus far been identified. Today the physics of cancer are known; what remains is massive engineering.
Drug companies have long been targeting mutations like this one to develop compounds that will interfere with the defective biochemical gateways. There are hundreds of drugs that may have some effect against some of the mutations, which sounds like an abundance of riches–but it’s also an abundance of complexity. That’s one reason that the pharma industry has a 95% failure rate for new products and that half of Phase III trials–the last step before approval–don’t cut it. “If I have 100 different drugs I can use in combination, then 100 times 100 is 10,000. You can’t do 10,000 trials,” says Sharp. But which ones can you do and should you do and on which patients?