Cancer is a malfunction or abnormality of cells in different parts of our body. It can occur in many organs such as lung, liver and kidney, but not in all: for example, cancer rarely occurs in the ankles or eyes. Some writers have suggested that cancer represents a group of diseases, and it is true that cancers behave differently depending upon the type of cancer and the organ they affect. However, all cancers share three basic characteristics: unregulated growth, lack of differentiation, and the capacity to metastasize to neighboring tissues.

Cancer "manifests itself as a population of cells that have lost their normal controls of growth and differentiation." Cancers share these three traits, though the extent of each may vary. Some cancers are highly metastatic meaning they move quickly to other parts of the body, while others move slowly over years or even decades. Cancers are categorized based upon these three characteristics, the extent of growth, differentiation, and presence of metastasis.

1.11 Unregulated Growth

Cell division and replacement is a normal process in the body. Cells in some parts of our body are constantly growing like fingernails and hair. Other areas are not growing bigger, but the cells within them are multiplying. Thus, while one characteristic of cancer cells is their ability to multiply, normal cells do that too:

"Cells do all kind of things, including divide into more cells: one cell can divide into two cells, each "offspring cell" can divide into two cells, and so on. Cell division occurs at various times and for various reasons: cells divide during the growth and development of the embryo and the fetus, for example, and when there is a need to repair an injury in the body, such as a scraped knee. Cells also divide in cancer_ cancer occurs when they divide out of control "(2)

1.112 Why Cell Growth is Necessary

Cell growth is needed because almost all parts of the body are subjected to daily wear and tear that kills or damages cells. Growth is needed to replace or replenish cells and sometimes to perform specific functions. For example, cells in our immune system grow to kill certain germs. As a child grows to an adult and increases in size, there is clearly cell growth and duplication. Cell growth and duplication are normal and necessary functions in our body. While normal tissue enjoys a careful balance where cell growth and duplication occurs when cells die or for other specific reasons, cancerous tissue may simply grow. Unregulated growth means a tumor grows without regard to the needs of the tissue or the normal controls for that cell or gene. One text explains:

"In the first stage, a normal cell undergoes an initial genetic change which partly releases it from the normally very stringent controls imposed upon its growth potential; the daughter cells accumulate further genetic mutations which accentuate this loss of normal growth regulation, until a population of tumor cells emerge which no longer respond to normal signals preventing cell division and growth. The cells of the primary tumor are, therefore, said to be growth transformed. The genetic mutations which accumulate in these primary tumor cells are to members of two classes of cellular genes, the proto- oncogenes and the tumor supressor genes. These genes control the ability of cells to pass through the cell cycle and, hence, their ability to divide or, alternatively to stop dividing and to undergo {differentiation] "(1)

The theme of this book is not that cancer is unusual or strange behaviors of cells, but normal behavior either expressed to an extreme or in an incorrect context.

1.113 Common Characteristics of Cancers

To call the growth of cancer cells completely unregulated or unpredictable is inaccurate. Tumors share certain characteristics. We know that some types of tumors grow rapidly, like small cell cancer, while others grow very slowly, such as the carcinoid tumor. We categorize different types of lung tumors based primarily upon their growth characteristics. There are two main categories of lung cancer small cell and non-small cell. Small cell tumors grow rapidly but are susceptible to chemotherapy while non-small cell tumors grow more slowly. Chapters 3-5 discuss how and why lung cancers are categorized.

1.12 Differentiation

Normal cells are differentiated, that is constructed or organized for a specific purpose. As a cell changes, it loses some of its distinctive characteristics, i.e., its differentiation. Cancer cells are classified from well-differentiated to poorly differentiated, with the degree of differentiation one indicator of how the cell has changed. Under a microscope, a pathologist can look at the cell, determine and categorize its differentiation. Tumor cells are labeled from well-differentiated ( meaning relatively limited changes have occurred) to poorly differentiated, meaning significant changes have occurred. The extent of differentiation is one factor in evaluating the status of the patient, but has not become a critical factor. Instead the extent of metastasis, or movement to other tissues, has become the chief factor in determining the status of the tumor and the treatment which will be administered.

Probably the most serious danger in cancer development is the tendency of cancerous cells to metastasize, that is, invade neighboring structures, and transmit the cellular malfunctions to those cells:

"Whereas a benign tumor will expand in size as a consequence of cell division, it will not invade surrounding tissues nor will it shed cells that are capable of initiating tumor foci elsewhere in the body. A malignant tumor will, however, actively invade and destroy surrounding tissue and also give rise to cells which often spread to produce foci of tumor growth at distant sites. Vile, Cancer Metastasis: From Mechanisms to Therapies 101-102. (Wiley & Sons 1995).

Metastasis is not strange or unique behavior, but essentially cells misusing certain inherent traits. Imagine if someone’s leg suffered a serious burn or injury. The body would likely repair the leg by replenishing cells and repairing damaged sources of blood supply. With a cancer, the body believes the area is damaged, so it connects with neighboring sources of blood and nourishment to replenish the damaged area. In truth, many cancers do reflect damage to DNA, but the remedy the body creates simply spreads the cancer, rather than repair the damage.

1.15 Analogies to Behavior of Normal Cells

Metastasis, the movement of cancer cells to normal organs and structures seems strange. Yet analogies to the behavior of normal cells are seen:

"It is also important to remember that expression of invasion promoter genes is not a purely pathological phenomenon seen only in cancer. Certain normal cell types demonstrate different elements of the phenotype as part of their usual functions. Thus, leukocytes resemble metastatic cells in many ways since they must leave the bone marrow and move, via the circulation to specific sites elsewhere in the body where they must penetrate to sites of infection and inflammation. Similarly, embryonic cells must move between developing tissues in a way that can be likened to tumor cell invasion.... Therefore, expression of the invasive phenotype by cancer cells should be thought of more as the activation of normal cellular programmes in an inappropriate cellular context, than as the expression of completely novel phenotypes. In this way, it may be possible to understand how and why the genes of invasion are expressed so aberrantly in tumor cells and, therefore, to generate more mechanism-based and effective treatments." Vile, Cancer Metastasis: From Mechanisms to Therapies 24 (Wiley & Sons 1995).

1.151 Summary of the Metastatic Process

Here is a short summary of the metastasic process:

1) Cancer cells located in an organ such as the lung manage to break down the barrier confining them to that organ. "Local invasion by tumor cells involves the activation of genetic programs which allow them to pass away from the confines of the primary tumor mass, through any surrounding tissues and eventually to reach of blood or lymph vessel." Vile, id.

2) The tumor cells then move to an adjoining lymph node or blood vessel, with the tumor establishing a source of blood supply in that new location.

1.16 Tumors Are Categorized Based Upon the Extent of Metastasis

Cancers are categorized primarily based upon the extent of metastasis. Non small cell lung cancers (the largest type of lung cancer) are classified from stage 1 to stage 4. Stage 1 tumors are limited to a defined area in a single part of the lung. Stage 4 means the tumor has metastasized to another organ, with stages 2 and 3 asessing the extent of movement to adjoining or distant lymph nodes. Stage one cancers are usually treated with surgical removal of the tumor, while stage four metastatic tumors treated with chemotherapy.

1.17 Metastastic Cancer Cells Retain the Characteristics of the Original Organ

One writer explains:

"even though cancers enlarge, invade adjacent body parts, and travel to distant metastatic locations, they remain unchanged. The characteristics of human tumors, with rare exceptions, are fixed for the life of every tumor, regardless of where or when distant metastases of the tumor are found. In 1874, Dr. W. Moxon, an English pathologist, described rectum in liver, referring to rectal tumors that were growing in their original unchanged forms after metastasizing to the liver.... a prostrate tumor that is diagnosed early prostrate specific antigen (PSA) was detected in the blood will continue to produce PSA years later at a metastatic site." Dermer, The Immortal Cell (Avery Pub. Co. 1994).

1.31 Proto-Oncogenes and Oncogenes

"the beginnings of cancer lay not in a wholesale rewiring of the cell, but in a subtle alteration of a fistful of key genes among the human quote of DNA. Under normal circumstances, such genes play a vital, growth-related role in all or most tissues of the body. In some tissues, the genes may set up the rounds of simple division, helping skin cells to proliferate into a scab around a wound, or allowing the immune system to send out a host of antibodies to assail an invading pathogen.... Whatever their assigned tasks, the genes that scientists have designated oncogenes share a common characteristic: they are vulnerable to mutations. And once mutated, the genes contribute to the birth of a tumor. That’s why the genes are oncogenes; onco is from the Greek onkos meaning mass. Some scientists prefer to say ‘protooncogene’ when referring to the healthy progenitor of a cancer gene, but most biologists rather imprecisely say oncogene for any gene that is prone to becomeing tumorrigenic. Nevertheless, it’s important to keep in mind that our cells possess oncogenes not because some nasty natureal or supernatural force place them there to keep our population in check, but because the body requires the genes to grow."

Angier, Natural Obsessions 5 (Mariner Books 1999)

It’s somewhat like an eight year old boy playing baseball in the house, a normal activity performed in the wrong context where it can do substantial harm.

1.32 How Oncogenes are Categorized

We have identified a number of proto-oncogenes and oncogenes. The term oncogene derives from the Greek term onco, meaning mass, and cancer is a mass of abnormal tissue. We know from our discussion of chromosomes that genes and oncogenes can be identified with a specific location such as chromosome 17. Oncogenes are also given specific names, which are usually three letter abbreviations such as myc, erb, or P53. Sometimes a prefix will be added such as v, for virus, indicating that the oncogene is associated with a virus, or c, indicating that the oncogene is associated with a chromosome defect.

1.33 The Two Types of Oncogenes: Growth and Tumor Suppressor Genes

There are two types of gene mutations which essentially combine to create a cancer. The first, is an abnormality of a gene involved with growth. An example is a gene that produces a protein that causes a growth_factor receptor on the cell's surface to be constantly on when in fact no growth factor is present. Thus the cell receives a constant message to divide.

The second type of gene which turns off the cell cycle and helps control cell growth is called a tumor suppressor gene. When the tumor suppressor gene malfunctions, the signal to the gene to stop duplicating is lost. Imagine a car. A car would travel when it wasn’t supposed to if the accelerator was on ( growth-factor gene) or if the brakes were not functioning, (tumor-suppressor gene).

1.34 How Do Cells Know When to Divide:

Cells divide only when they receive the proper signals from growth factors that circulate in the bloodstream or from a cell they are in direct contact with. For example, if a person loses blood, a growth factor called erythropoietin which is produced in the kidneys, circulates in the bloodstream and tells the bone marrow to manufacture more blood cells. Growth factors that come from outside the cell can transmit a message by binding to the appropriate receptor on the cell triggering a signaling system that activates a specific gene in the cell's nucleus. Other signals generated within the cell itself can use the signaling system to activate a gene.

1.41 DNA Damage

1.42 Time for Cancer to Develop

1.52 Complete Response and Partial Response

The term complete response means elimination of the cancer, at least based upon available medical tools of measurement. It unfortunately does not preclude reappearance of the disease. The term partial response, as used by most authorities means a 50% reduction in the size of the tumor. The initial chemotherapy is called first-line chemotherapy; if the chemotherapy is needed again, that is second-line chemotherapy. Since there the cells develop some immunity to chemotherapy, there may be some different considerations with second line chemotherapy.

1.53 Lymph Nodes

1.53 Regional and Other Lymph Nodes.

In staging the patient, that is ascertaining his status, doctors consider whether the lymph nodes are cancerous, and where the cancerous nodes are located. The spread of a tumor to a lymph node located near the tumor, or a regional node, is less serious than the spread to one further away, a contralateral node. If the lymph node is further from the tumor, that indicates a greater spread of the tumor.

1.54 Blood Vessels

A tumor may also spread through the body through a blood vessel. There are various tests to ascertain the extent of cancer in the blood however, blood vessels cannot be individually assessed as lymph nodes usually are. A surgeon will generally obtain samples or biopsies from lymph nodes to ascertain whether the nodes are cancerous. This is important because as we will see in chapter 4, the type of treatment given depends upon lymph node status.

1.55 Carcinomas and other Forms of Cancer

The most common type of cancer is a carcinoma, a cancer that arises in the cells that forms the lining of different parts of the body. Cancers in the lung, breast, prostrate, and colon are all carcinomas. Cancers that involve tissue or bone are called sarcomas. Cancers involving blood cells are known as lymphomas or leukemias. While most research is organ specific, some studies will cross organ lines. Some forms of chemotherapy for lung cancer are also used for breast or colon. Scientists are less likely to test a treatment on other types of cancer.