Life is an emergent property, something more than the sum of its parts, the irreducible product of complex relationships between inanimate components. After all, we are made of the same stuff as the dead matter around us. But how are we so different? An analysis of our bodies the minute before versus the minute after we die would not show many differences in our atomic, molecular and cellular composition. But the relational status at every level of organization would be drastically different. It's the relationships among our parts that keep us breathing, eating, thinking and loving.
Cancer is a disease of poor relationships. While our bodies are harmonic societies of cells, cancer is a riot. A handful of random mutations in a few genes is all it takes to create a massive shift in the relational status of our proteins, our cells, our organs. Minute molecular changes create a ripple effect throughout the various relational planes of our bodies, and these changes can eventually kill us. Our tumors are flesh of our own flesh, remarkably similar in composition to our healthy tissue, a flesh that is too alive for our own good, a flesh with new and undesired emergent properties.
We have known the emergent properties of cancerous tissues for a long time. The Greeks used their word for "crab" to describe a tissue with many legs, a tissue that moves and invades. It's also a tissue that grows rapidly, that survives harsh conditions; it's a bloody tissue that consumes a lot more nutrients than normal.
During the past 40 years, we cancer researchers have identified and studied a few hundred genes (out of tens of thousands in the human genome) that, when mutated, can generate the malignant emergent properties. We divide these cancer genes in two categories, oncogenes and tumor suppressor genes, depending on whether they promote or slow down cancer, respectively. Some oncogenes increase cell proliferation, others allow cells to survive nutrient deprivation, others turn static cells into nasty little travelers. We have been studying these cancer genes with maddening passion. We have published more than 50,000 peer-reviewed papers on a single tumor suppressor gene called p53. We believe that understanding these cancer genes in great detail will reveal the way to cure cancer. In the process, we uncovered a humbling, often overwhelming fact: our tumors are all driven by unique combinations of mutated cancer genes.
Tumors are Darwinian entities. They obey the basic rules of evolution: random mutations create genetic diversity; the fittest cells survive and reproduce more than the unfit; the cell population in the tumor evolves around the selective pressure of the day. Tumors evolve around the physical boundaries imposed by the neighboring healthy tissue, around the lack of oxygen in their cores, around the immune system and around our crude poisonous therapies. A cocktail of poisons may kill most of them, and we poison our friends and relatives with the hope that the tumor will go extinct. However, the cells that survive are likely to be resistant and the tumor often comes back as an evolved, more lethal version of itself. These cancer cells never cease to surprise me, their survival instinct matches ours. They are addicted to life and create addictive relationships with our healthy parts, taking it all and giving none, creating havoc all around.
Just like the wings in birds and bats, which arose from different evolutionary beginnings to enable the flight of reptiles and mammals, our tumors will follow different molecular paths to survive against all odds. The pathologist may say that our tumors are of the same grade and stage, but this is a low resolution view, they are nonetheless driven by a different combination of mutations in cancer genes. The chances that, from a restaurant menu of 20 appetizers, 40 salads, 100 entrees, 20 desserts and 100 wines, you and I would order the exact same combination are vanishingly small. So it is with tumors and their mutations in cancer genes.
Enter Personalized Medicine. Human ingenuity to the rescue. The solution goes like this. First, we are developing ways to find out what the combination of gene mutations is in every tumor. We call this discipline Molecular Diagnostics. Second, we are developing a collection of "smart" drugs that specifically inhibit each oncogene or activate each tumor suppressor gene, perhaps as few as a few hundred drugs in all. We call these Biologically Targeted Therapies. Molecular Diagnostics can then be used to interrogate the tumor about what its combination of mutations is. We can take this list to the kitchen full of ingredients, and return to the patient with the right cocktail of Biologically Targeted Therapies, one that will lock the tumor into an evolutionary dead end and send it to extinction.
The vision of Personalized Medicine fuels me and many other cancer researchers. This paradigm organizes our efforts, funnels our energies and keeps us motivated to tackle the most difficult scientific challenge of our age. There are weak spots in this paradigm, but it currently looks like the best shot we've got. We are not there yet, but much progress is being made for specific cancer types. It will take a lot more effort and money to see this vision realized. We cancer researchers will put in the effort -- let's hope that government and society will come up with the money.
In order to succeed we will also have to radically change the way we practice medicine. Matching macroscopic symptoms with standardized drugs just won't do. Each cancer patient is a new scientific problem.
So remember this: each one of our tumors is unique, as unique as each of us. If you are a cancer patient, ask your doctor about what Molecular Diagnostics and Biologically Targeted Therapies may be available for your tumor type. Inquire about current clinical trials employing this paradigm.
I am a Joaquin Espinosa, a cancer biologist. Please help me and other cancer researchers make this battle a personal one.
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