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Cancer Is Survival of the Fittest
Nature dictates that in any environment, survival is awarded to those best suited to it. The physical and mental capabilities of any species are determined largely by their DNA. Cancer can also be thought of as abiding by this principle of survival of the fittest, a phrase coined based on the work of Charles Darwin. A cancer survives only by generating cells that are fit enough to grow in the face of the body’s restrictions (listed above) and the arsenal of cancer-fighting therapies to which we subject it.
Another word for a cancer cell is clone. When new cancer cells or clones are generated inside a tumor, some will be hearty enough to survive and others will not be. The heartiest ones will expand in number until they encounter something that limits their growth, such as a cancer-fighting drug. If some cells survive the treatment, then it is mainly because their DNA contains the necessary alterations that help them resist the drug; this population of cells will then expand, and the composition of the cancer will again change.
Thus, the makeup of a cancer is dynamic, punctuated by periods of growth and periods of dormancy, responsive both to random changes to its DNA and to the changing nature of its environment. This propensity of cancer cells to adapt, just like living species in nature, has been termed clonal evolution. Clonal evolution enhances a cancer’s range of abilities and explains a great deal about its behavior. For example, when a cancer returns after being declared in complete remission, it is because a few cells were different enough to stay alive after a treatment killed nearly all the other cells; this difference could have been present from the start of treatment or it could have developed as a response to it. Whichever occurred, it is cancer’s ability to diversify and adapt its DNA that enables it to survive.
We can now answer the essential questions: it is by virtue of cancer’s propensity to change-changing DNA, leading to cells with new abilities-that a polyp goes through its cancer sequence and that any cancer first develops and then behaves the way it does in the body.
The Devil Is in the Details
The types of changes to DNA that enable a cancer to grow, survive, and evolve can be understood by describing the development of colon cancer. The first DNA mutation that starts a cell on the long road to becoming a colon cancer is caused by a combination of environmental factors (such as a diet low in fiber and high in red meat) and a person’s genetic makeup. With additional genetic changes, a benign polyp emerges. Further changes cause the polyp to be converted into a cancer. Still more mutations to DNA enable the mature cancer to leave the confines of the colon and spread to lymph nodes, the liver, and other locales. The conquest of cancer begins with the precise understanding of these changes to DNA, a fact not lost on science’s brightest minds.
Dr. Bert Vogelstein and colleagues have pioneered our understanding of the genetic changes that bring about cancer. They have clarified that most cancers proceed according to a genetic model in which each step on the road to cancer is accompanied by additional DNA alterations. Many of these alterations involve the activation of oncogenes and loss of tumor suppressor genes, which I described as being central to the development of every cancer.
The multitude of DNA changes that characterize cancer explains why the disease often needs to be treated with more than one drug: many methods of attack are needed to hit so many different targets. For example, a patient with advanced colon cancer today may receive up to four medicines as the initial effort to control the disease: three chemotherapy drugs (5-FU and leucovorin plus either irinotecan or oxaliplatin) plus bevacizumab (Avastin), a targeted therapy that alters blood flow to a tumor. Ongoing clinical trials are testing the addition of still more drugs to the standard four-drug colon cancer regimen. In the future colon cancer treatment may involve the use of five or six drugs in an attempt to eliminate every last cancer cell.
The treatment of other cancers is following suit. The addition of newer targeted drugs to traditional chemotherapy is leading patients to have a better quality of life, longer survivals, and more cures. Also, the addition of radiation therapy to chemotherapy (chemoradiation) to fight cancers that are difficult to cure surgically, such as stage III cancers of the lung, pancreas, and esophagus, provides a multipronged assault on cancer’s many deranged pathways of growth and survival. Sometimes, and in particular with cancer, you have to fight fire with fire. Cancer’s development has both organized and chaotic aspects. As chaos affects its genetic makeup, a cancer generates a diversity of cells with varying abilities. Ultimately, some cells may spread and cause metastases, the greatest challenge to survival.