Cancer Information

What is Cancer?

Taken from Dr. Bruce Feinberg’s Breast Cancer Answers

Cancer occurs when cells in the body change and grow out of control. Usually, the multiplying cancer cells form a lump called a cancerous tumor. Cancerous tumors are also called malignant tumors. Sometimes malignant tumor cells can break away from the mass and travel through the bloodstream or lymphatic system to other parts of the body. This process is called metastasis. Not all tumors are cancerous. Those that are not are called benign. Cells from benign tumors do not spread to other parts of the body.

Cancer is the most complex of human diseases. It begins with a step-by-step transformation of a single human cell. Because there are over 200 types of cells in the human body, over 200 types of cancer exist, each one distinct.

To understand cancer and its treatment, you have to understand that animals are made from cells, that cells can transform and grow out of control, and that medicines are available that can kill these transformed, bad-behaving cells without harming the good cells that keep us alive.

1. The Cell
2. Carcinogenesis
3. Genetics
4. Invasion and Metastasis

The Cell

The Lego is the perfect metaphor for a cell. In Legoland, the Lego is the basic building block. Hundreds of different types of Legos when appropriately combined can create an infinite variety of structures. You can take Legos of just one variety and stack them side by side and up and down to create a wall. Add two windows and a door, and create the completed front wall of a house. After a child builds three sidewalls and secures them with a floor and a roof, the house takes on a recognizable appearance.

While the Lego is the basic building block of Legoland, the cell is the basic building block of organic life (living creatures). The cell is called the origin of life because animals grow from a single cell made by the joining of sperm and egg. One cell gives rise to the billions of cells that make the complete animal. Like Legos, the billions of cells are not identical in appearance but rather fall into a few hundred different types: hair cells, skin cells, blood cells, etc.

The formation of the human body, like any mammal’s body, begins with the meeting of a sperm and an egg. The sperm fertilizes the egg, which creates the first cell, the beginning of a human body. This cell then divides to make two cells. Two cells divide to make four, and then those cells continue to divide until there is a cluster of cells. Initially all of the cells in the cluster are identical. Next these identical cells begin a process in which they become the more than 200 different types of cells that make the human body complete. This process is called differentiation; the cells differentiate or become different types. This early developing human is called an embryo.

The process of differentiation in the developing embryo begins with these clustered cells organizing into three layers: an outer layer called ectoderm, an inner layer called endoderm, and a middle layer called mesoderm. The outer layer, ectoderm, differentiates into skin and nerve cells. The middle layer, mesoderm, differentiates into blood, muscle, and bone cells. The inner layer, endoderm, differentiates into the cells that compose all of the body’s organs.

Imagine Legoland being alive. In the beginning, there was one small, rectangular, white Lego. Then there were a bunch of small, rectangular, white Legos; then white Legos morphed into three groups—white squares and red and blue rectangles.

Primitively speaking, all of your body’s organ cells begin with the endoderm layer: they have a common origin and are structurally similar. This is a very important point, as we will later see. As these primitive cells further differentiate and mature, their structure and function assume that of adult cells. Mature cells progress from individual cells to sheets of cells. The sheets of cells then organize to form tissues. Different types of tissues combine to form organs. Finally, the organs are arranged within a musculoskeletal framework supported by a circulatory and nervous system.

Returning to our Legoland metaphor, the white, blue, and red Legos have now morphed into hundreds of different types. There are billions of each type, trillions of Legos in all. Some Legos have been assembled into a wall (like sheets of cells forming tissues). Doors and windows have been added to the wall to make the front of a house (like an organ), and roofs, floors, walls, and more have been organized to make a complete house (like a complete human being).

Carcinogenesis

Throughout your lifetime cells are continuously injured and repaired. Bruises, scrapes, cuts, burns, infections, chapped lips, and tongues burned by pizza cheese and hot coffee are a sample of the myriad of everyday cellular injuries that you experience. Your body has the remarkable ability to repair this cellular damage and does so in a constant, ongoing process. Some cellular damage is below the surface, caused by the tobacco smoke that we inhale, the chemicals in the food that we eat, the radiation from the sun, and the internal (natural), physical, chemical, and hormonal stresses that are part and parcel of being alive. Sometimes, if the injuries are chronic or recurrent, or if there is a genetic predisposing defect, the body is unable to repair the cellular injury. The body’s failure or inability to repair cellular injury can lead to cancer. The process by which the failed repair of cellular injury leads to cancer is called carcinogenesis.

In the last section, I mentioned that all of the body’s specialized organ tissue has a common origin in the cells of the endoderm of the developing embryo. As these primitive cells mature, they retain certain common features, giving organ tissue a similar appearance under the microscope. The microscopic appearance is often referred to as glandular, which means something different than what you might think. To a pathologist, glandular tissue refers to a group of cells that are organized so that they can either take in nutrients (absorb) or release chemicals needed to maintain normal body function (secrete). The cell type common to these glandular tissues is called an epithelial cell. The epithelial cells are flat where they connect the organs to the outside, such as at the mouth and anus; are cube shaped in the organs that are secretory, such as the breast, prostate, and pancreas; and are an elongated cube or column shaped in the organs that absorb nutrients, such as the colon and small intestine. When flat epithelial cells transform into cancer, they are called squamous cell carcinoma. When cuboid or columnar cells transform into cancer, they are called adenocarcinoma.

At this point you might be thinking, “I’ve lived a healthy lifestyle. How can I have cancer?” I advise a deep breath and patience because I am about to explain how normal, everyday stress can cause cellular injury and initiate the cascade of events that result in cancer. In order to understand the how and why of carcinogenesis, one needs to understand the inner workings of a cell—its genetic code.

Genetics

All human cells have a similar design: an outer membrane covering a gelatinous liquid cytoplasm within which is a central core structure, the nucleus. The image is that of a Tootsie Roll Pop where the wrapper is the cell membrane, the lollypop candy is the cytoplasm, and the Tootsie Roll is the nucleus. Within the nucleus resides the blueprint or operating code of not only the cell but also of the entire organism.

Like computer software written in special binary code, the operating code of living organisms is written in a special language called DNA, which is actually a chemical code comprised of four characters called nucleoside bases. DNA is a unique code language that, once translated, instructs the cell to build proteins. Proteins are the cell’s machines that bring food into the cell, remove waste from the cell, repair the cell after injury, prepare the cell for growth and division, etc.

Like many other types of machines that we are more familiar with, proteins may have many different functions but are all structurally related. Automobiles, tractors, speedboats, and helicopters are very different forms of transportation but are all propelled by an internal combustion engine. Refrigerators, blenders, washers, and coffee grinders are very different appliances, but they are all powered by an electric motor. Computers, cell phones, digital cameras, and CD players perform different functions, but they are all controlled by a microprocessor chip. Like each of these examples of inorganic machines, proteins are the workhorses of organic machines and the cells that comprise them. The blueprint for each protein is encrypted in the DNA code.

By definition, a code must be broken or translated for the encrypted message to be understood. The DNA message for protein building requires not only translation, but it must also get transported from the nucleus to the cytoplasm where the proteins are manufactured. The translation and subsequent transport of the encrypted DNA message is facilitated by another nucleoside base language called RNA. The DNA message is translated to RNA, which leaves the nucleus and travels to the cytoplasm where it docks with a structure called a ribosome, the protein-manufacturing factory.

The chemical building blocks of proteins are called amino acids. The amino acids are chemically linked one to another according to the instructions of the DNA message. Let me try to summarize in a single statement: Amino acids in the cytoplasm are assembled into proteins by the ribosome under the direction of an RNA message, which is the translation of a DNA code sequence from within the nucleus.

A complete DNA sequence that encodes a protein is called a gene. Genes are clustered into long strands of DNA called chromosomes, which are made even longer because these genes are also separated from one another by non-message base sequences. There are 46 chromosomes in a normal human cell, 23 contributed by the father via the sperm and 23 contributed by the mother via the egg. The chromosomes are arranged in 23 pairs. Scientists now believe that there are between 20,000 and 40,000 genes necessary for human life, making it likely that there are approximately 1,000 to 2,000 genes per chromosome pair.

Think of this genetic operating system or genome as the body’s complete information encyclopedia or better still, the body’s owner’s manual.  Everything needed to build, operate, and repair the body is written in the manual, a copy residing in each cell.   The encyclopedic size owner’s manual is comprised of 23 volumes (chromosome pairs), each 1,000 - 2,000 chapters long (genes) composed in a four-character code language (DNA) requiring billions of characters (nucleoside bases) in all. This is worth repeating, every cell in the body has the complete manual of information (genome) stored in its library (nucleus), but only certain volumes are off the shelf at any one time, opened to specific chapters as the genetic needs dictate. Genes for hair color would not be turned on in blood cells, and genes to produce hemoglobin would not be turned on in hair cells. Beginning in the embryo and throughout cellular differentiation, fetal maturation, growth, and development, messages are turned on and off in a complex system of signals and responses. For the messages and signaling to work properly, every cell needs to have its billions of characters (nucleoside bases) in the correct sequence, ready for the moment when one of the volumes is taken off the shelf and opened to a chapter to be translated. A mistake in a base sequence is called a mutation.

Mutations can occur in a variety of ways. Let’s use that encyclopedic owner’s manual metaphor to illustrate the point.  Sometimes information passed on from a parent is incorrect, causing some of the chapters to have wrong information. Such genetic mutations are called hereditary mutations. Sometimes there is a misprint at the factory (embryo or fetus), leading to incorrect information in some of the chapters. Such genetic mutations are called congenital mutations. Most commonly, the original information and printing are correct, but from years of use and handling, print becomes smudged, paper stained, or pages torn, leading to incorrect messages. Such genetic mutations are called acquired mutations.

Genetic defects or mutations that cause a cell to reproduce uncontrollably and invade surrounding structures are what cause cancer. Many forms of cellular injury like those caused by chemicals and radiation lead to the types of mutations that cause carcinogenesis. Acquired mutations rarely occur from a single insult but rather from repeated insult and injury like years of tobacco use, chronic irritation from fecal waste, decades of cyclic hormonal stress, or just living. Thus, all cancers are consequences of genetic mutations, but few, approximately 10%, are hereditary. Most cancers are the result of acquired genetic mutations.

The majority of adult cancers most often occur in the sixth, seventh, and eighth decades of life and are predominantly the result of acquired mutations brought about by years of cellular stress and injury. The transformation to cancer is slow, taking years or decades as gene after gene is mutated until one day the mutations are extensive enough to meet the criteria that define cancer. The most serious mutations are those that confer on a cell the behaviors of invading surrounding structures and spreading through the blood and lymph circulations. 

Invasion and Metatases

What makes invasive cancer more problematic is the possibility of cancer cells entering into the blood. As the invasive cancer grows through or infiltrates the layers beneath the cells, root-like projections of tumor may also grow through or infiltrate the wall of nearby blood vessels. Once exposed to the bloodstream, cancer cells may break free from the growing cluster (tumor) gaining access to the blood circulation as it flows through the body.

If individual cancer cells or cell clusters survive in the blood circulation, they may adhere to or anchor to the wall of a blood vessel anywhere in the body and there begin a new nest of growing cancer cells. This nest may then invade through the blood vessel wall. The nest may then extend into the organ in which that blood vessel is located (the lung, the liver, etc.), forming a cancerous tumor in that organ. The nest of cancer cells anchored into a blood vessel of another organ where it then forms a cancerous tumor is what doctors call a metastasis.

The overriding concern for the patients with infiltrating or invasive cancer, and the doctors who treat them, is whether cancer cells have escaped into the circulation and might develop into metastases. The mission of the medical oncologist, like me, is to determine the risk of metastases in order to either do something preemptively to destroy the escaping cells before they anchor, nest, and/or invade another organ (adjuvant therapy) or to treat the metastases if they can be identified or are readily apparent (metastatic therapy).