Findings: Understanding cancer

Two years ago, I had the pleasure of interviewing professor Randy Pausch for an alumni article about the Entertainment Technology Center. In the recent wake of his exuberant and downright remarkable approach to his pancreatic cancer diagnosis, I wanted to explain, to the best of my ability, what cancer is, and why it is so difficult to target.

An adult human body contains approximately 10 trillion cells. These cells grow and divide in an orderly manner. When old cells die, new cells proliferate to take their places. This is an interesting point, and has important implications for cancer. The cells in the human body are in flux. They are constantly maturing, multiplying, and dying. To the naked eye, this turnover is undetectable because the body kills unnecessary cells and replaces missing ones so quickly that the body’s overall cell count appears unchanging.

Imagine a company that hires and fires employees at a faster- than-normal rate. Within minutes of an employee being fired, another employee appears by the cubicle to take his spot. Over the course of a week, the staff number at the company is the same, but the employees are all new. The same applies to the cells in the human body. In order for the body to maintain this perfect balance in cell number, the cell’s life cycle has to be strictly regulated.

Going back to the company, imagine it loses its firing department to the flu. The firing department is sick, and cannot execute orders to fire employees, but the company is still hiring. Eventually, the building will be swamped with employees. Desperate for space, they crawl into the ventilation ducts, hang from the rafters, and occupy closets and bathrooms. The hiring department is hiring out of control because there is no firing department to counterbalance it. The company has cancer, and if the problem is not fixed, employees will smash pipes, shatter windows, and break down walls until the building collapses.

The biological mechanism for this is fairly simple. The heart and soul of a cell is its DNA. A single piece of DNA contains all the information necessary to encode every single protein in the body.
In order for a cell to divide into two cells, it has to split this DNA into two copies — one for each cell. If the cell approaches its first checkpoint with faulty DNA, the birthday party is over. It cannot proceed to the next phase in its life cycle until its DNA is repaired. Faulty DNA contains mutations, or errors, in the code.

As such, several proteins encoded by the DNA will also be faulty. This is bad, because some of these proteins are responsible for cell division. There is one protein chiefly responsible for regulating cell cycle control. In 1993, it was named Science magazine’s Protein of the Year. The protein is called p53, and it stops the cell containing faulty DNA from dividing. In addition, p53 also recruits the enzymes necessary to repair the DNA. If the damaged DNA is not fixed, p53 targets the cell for destruction.

Thus, p53 takes the role of the hiring and firing departments. As such, one of the most prevalent mutations leading to cancer is in the gene that makes p53. Because of its role in cell cycle regulation, p53 is called a proto-oncogene. When proto-oncogenes contain a mutation, they become oncogenes. Oncogenes cause cells to divide wildly and dangerously. If inherited, they can sometimes (but not always) give rise to cancer.

A second group of genes, tumor suppressor genes, is also important in cell-cycle control. Tumor suppressor genes code for proteins that inhibit cell growth. Like proto-oncogenes, defects in tumor suppressor genes give rise to cancer.

Out of the roughly 35,000 genes in the body, only a small percentage of genes (the proto-oncogenes and the tumor suppressor genes) are related to cancer — p53 is a remarkable protein that functions as a tumor suppressor gene and a proto-oncogene. Mutations in either set of genes can be inherited, or they can occur through environmental exposures to carcinogens.

A well-known oncogene is RAS, which is found on chromosome 11. Thirty percent of all tumors have a mutation in RAS. MYC is an oncogene associated with Burkitt’s lymphoma, a cancer of the lymphatic system. Hereditary breast cancer results in inherited mutations in the tumor suppressor genes BRCA1 and BRCA2.

Sometimes, cells contain mutations. Almost all of the time, the mutations are repaired. In rare cases, particularly bad mutations (mutations in the cell cycle) pass on from cell to cell. These cells form a tumor. Because cancerous cells can appear at any given time, and with no warning, the only current treatment of cancer is chemotherapy, which kills rapidly dividing cells. But cancer must exist as a clump of hundreds of cells exhibiting abnormal growth (a tumor) before it can be seen — making the individual targeting of cancerous cells impossible.

In the cancerous company, the employees will eventually die of starvation. The problem arises not when the employees are swarming the building, but when they are given food and water to survive. This is angiogenesis, and it is the process a tumor goes through to find nearby blood vessels to feed itself. Without this blood supply, the tumor cannot spread, or metastasize. It is benign.

Put another way, uncontrolled cell growth is only mildly bad until it hunts out blood vessels to sustain itself. When a tumor recruits blood vessels, it comes to life. Now cells can slip off the tumor and into the blood stream.

From here, they can latch onto any tissue in the body and start the process anew. Cancer has entered the building — and it is not leaving anytime soon.