Understanding Cancer Diversity
The human body operates, in essence, like a large, multicellular society. Within this tight-knit community, trillions of cells, organized into hundreds of different tissues, collaborate for the good of the whole organism. Some cells convert food into energy, some transport oxygen or nutrients throughout the body, some fight infections, and some shuttle the organism's genes into the next generation.
Cancer occurs when a single cell acquires the ability to reproduce aggressively and to invade other tissues. This rebellious cell shuns its normal role, instead multiplying and ultimately colonizing areas of the body where it doesn't belong. Left unchecked, this anarchy destroys the cellular society. It interferes with the body's normal function, destroys organs, and eventually kills the organism.
Once cancers have spread, they are difficult to eradicate because cancer cells come from the body itself. The body's immune system is unable to distinguish cancer cells from normal ones. Antibiotics are uselessthey are designed to eliminate microbial invaders. Chemotherapy and radiation can kill cancer cells, but they also kill other cells in the body.
The search for a cure is complicated by the fact that cancer is not one disease. Physicians and researchers recognize at least 200 types of cancerthat's approximately as many cancers as there are types of tissue in the body. Although they share similar basic characteristicsthe ability to reproduce vigorously and to invade foreign tissueseach cancer is different in terms of its prognosis and treatment. Its properties depend on the type of tissue from which it arose and on which tissues it subsequently invades.
Although this diversity presents a challenge, it also offers hope. By learning about the molecular aberrations that drive cancers, researchers such as HHMI's Bert Vogelstein have enhanced our understanding of the basic biology of this group of diseases. What's more, they have developed techniques that will allow them to characterize individual tumorstools that in future should allow doctors to screen people for their predisposition to cancer, to detect tumors that are not yet visible, and to select the treatment most effective for eliminating a particular cancer.
What is Cancer?
Cancer cells share two basic properties. First, they proliferate in defiance of the normal constraints that keep cell growth and division in check. And second, they invade and colonize territories normally inhabited by other cells.
Cells that have the first property will divide over and over to form a small, self-contained mass called a tumor. Such tumors are considered benign because they are restricted to one site in the body and can usually be surgically removedcleanly and completelywith few complications.
But increased cell proliferation alone is not enough to cause cancer. A tumor is considered cancerous only if its cells have the ability to invade surrounding tissue, in which case it is said to be malignant. Malignant cells can break loose from the primary tumor, enter the bloodstream or lymphatic vessels, and form secondary tumors at other sites in the body. The more widely the cancer spreads, the harder it becomes to eradicate. This metastasis is what makes cancer so deadly.
Different Cells, Different Cancers
Any cell type can give rise to a cancersome even give rise to several different types. Cancers are generally classified by their tissue of origin. Sarcomas, for example, come from connective tissue or muscle. Carcinomas arise from the epithelial cells that line the body's organs. Hippocrates coined the name for this common type of malignant cancer from the Greek word for crab (karkinos), because physicians thought that these tumors resembled the claws of a crab.
Some 90 percent of human cancers are carcinomas. Why some cells are more likely to become cancerous than others is complex and not entirely understood. The tendency for any cell to develop into cancer undoubtedly involves its natural propensity for proliferation. Cells that divide more rapidly are closer to behaving like cancers than those that divide slowly or not at all. In addition, cells that are exposed to cancer-causing mutagensagents that change the nucleotide sequence of DNAare more likely to become malignant. Finally, cells that have trouble detecting and repairing damaged DNA are more likely to become cancerous. Such cells have a greater tendency to accumulate the mutations that promote the growth and spread of cancer.
Different Genes, Different Cancers
Scientists have identified hundreds of genes that are mutated in cancers, and each cancer is characterized by its own array of genetic lesions. Different combinations of genes are altered in different forms of cancerand even in patients that appear to have the same form of the disease. Certain genes always go hand in hand with particular cancers. Mutations in a gene called APC, for example, occur largely in colon cancers. Other genes, such as p53, are involved in a variety of human cancers.
Researchers are actively investigating why certain genes are associated with particular cancers. It might have something to do with how different cells use these genes. Each cell in the body, whether it is a heart cell or a liver cell or a blood cell or a brain cell, receives the same set of genes. But perhaps cells that line the colon rely heavily on APC to control their growth and proliferation, whereas other cells in the body have chosen different genes to perform that critical task. In the case of p53, perhaps all cells use this gene to monitor their DNA for damage and then decide whether to divide or self-destruct.
Finally, exposure to different cancer-causing agents can influence which type of cancer will form. For example, chemicals present in cigarette smoke cause specific kinds of mutations in the p53 gene. These lesions are frequently seen in lung cancer but not other kinds of cancer. Aflatoxin, a toxic molecule produced by a mold that grows on improperly stored peanuts and grains, generates a different mutation in the p53 geneone associated with liver cancer. UV radiation causes yet a different type of p53 mutation that is found in 90 percent of patients with skin tumors but rarely in cancers of the liver or lung. Tracing mutations to a particular carcinogen can alert health officials to the presence of cancer-causing chemicals in the environment, and appropriate measures can then be taken to eliminate people's exposure to these chemicals.
Is Cancer Hereditary?
For the most part, the answer is no. Cancer is a genetic disease in that it is caused by mutations that alter the function of our genes. Most of these mutations, however, are not inherited but occur after birth. Because these changes usually occur in body cells other than the sperm and eggs that carry the person's DNA into the next generation, they are not passed on. A portion of these genetic lesions result from interactions with cancer-causing elements in the environment, such as sunlight and tobacco smoke. Smoking is a major source of carcinogens. If we could eliminate the use of tobacco, we could prevent about 30 percent of all cancer deaths.
The majority of cancer-causing mutations, however, arise within cells without any help from outside agents. Cells can make mistakes while copying their DNA and then fail to repair them, for example. These genetic errors are a major source of the types of mutations associated with cancer.
That said, certain types of cancers can run in families. In this case, individuals inherit a mutation that predisposes them to developing cancer. Certain families, for example, carry a mutation that knocks out the activity of a single copy of the APC gene. Children in these families inherit an increased risk for developing colon cancer.
Thanks to our studies of cancer genetics, we now know that cancer is not a single disease but a collection of diverse yet related diseases. Our ability to determine which genes are altered in a particular tumor should help doctors tailor treatments to individual patients. Furthermore, the discovery that some of the same types of genetic lesions crop up again and again in different tumors suggests that there may be only a limited number of ways in which cancers can breach our cellular defensesand offers hope that we can develop therapies that will tackle these diseases.
© 2013 Howard Hughes Medical Institute. A philanthropy serving society through biomedical research and science education.