2. Classification of cancer cells

Cancer cells can be grouped into two general categories: non-blood-cell cancers (usually referred to as “solid tumors”) and blood-cell cancers. Solid tumors are further classified according to the cell type from which they arise. Carcinomas, the most common tumors in humans, are cancers of epithelial cells, and include lung, breast, colon, and cervical cancer, among others. These cancers generally kill by metastasizing to vital organs, where they grow and crowd the organ until it no longer can function properly. Humans also get cancers of the connective and structural tissues, although these “sarcomas” are relatively rare compared to carcinomas. Perhaps the best known example of a sarcoma is bone cancer (osteosarcoma).

Blood-cell cancers make up the other class of human cancers, and the most frequent of these are leukemias and lymphomas. Blood-cell cancers arise when descendants of blood stem cells, which normally should mature into lymphocytes or myeloid cells (e.g., neutrophils) stop maturing, and just continue proliferating. In a real sense, these blood cells refuse to “grow up” – and that’s the problem. In leukemia, the immature cells fill up the bone marrow and prevent other blood cells from maturing. As a result, the patient usually dies from anemia (due to a scarcity of red blood cells) or from infections (due to a deficit of immune system cells). In lymphoma, large “clusters” of immature cells form in lymph nodes and other secondary lymphoid organs – clusters that in some ways resemble solid tumors. Lymphoma patients usually succumb to infections or organ malfunction.

There is another way to classify human cancers: spontaneous and virus-associated. Most human tumors are called spontaneous, because they arise when a single cell accumulates a collection of mutations that causes it to acquire the properties of a cancer cell. These mutations can result from errors made when cellular DNA is copied to be passed down to daughter cells, or from the effects of mutagenic compounds (carcinogens) that are byproducts of normal cellular metabolism or that are present in the air we breathe and the food we eat.

Mutations can also be caused by radiation (including UV light) or by errors made in assembling the segments of DNA that make up the B and T cell receptors. As we go through life, these mutations occur “spontaneously,” but there are certain factors that can accelerate the rate of mutation: cigarette smoking, a fatty diet, an increased radiation exposure from living at high altitude, working in a plutonium processing plant, and so on.

In addition to mutations in cellular genes that can corrupt growth-promoting and safeguard systems, some viruses produce proteins that can interfere with the proper functioning of these same systems in virus-infected cells. Virus-associated cancers also are “spontaneous” in the sense that mutations are involved. However, virus-associated cancers have, as an additional accelerating factor, a viral infection. For example, essentially all human cervical cancers involve an infection by the human papilloma virus. This sexually transmitted virus infects cells that line the uterine cervix, and expresses in these cells viral proteins that can disable two safeguard systems, including the p53 system. Likewise, hepatitis B virus can establish a chronic infection of liver cells, can inactivate p53, and can act as an accelerating factor for liver cancer. So the net effect of an infection with these special “tumor” viruses is to decrease the total number of cellular genes that must be mutated to turn a normal cell into a cancer cell.

The hallmark of virus-associated cancer is that only a small fraction of infected individuals actually get cancer, yet for those who do, virus or viral genes usually can be recovered from their tumors. For example, less than 1% of the women infected with genital human papilloma virus will ever get cancer of the cervix, yet human papilloma virus genes have been found in over 90% of all cervical carcinomas examined. The reason for this, of course, is that the virus can’t cause cancer by itself – it can only accelerate the process that involves the accumulation of cancer-causing mutations. About one fifth of all human cancers have a viral infection as an accelerating factor.