Cancer 201—treatment basics

Once a cancer has been diagnosed, we must use our knowledge of biology, medicine, and clinical trials to plan treatment. Treatment can be curative or palliative (that is, with a goal of reducing symptoms or extending life, rather than effecting a cure).

Understanding cancer treatment requires a little bit of basic biology, and as with all of my more “science-y” posts, please forgive any oversimplification (but please also note that this complexity stands in stark contrast to the simplistic altmed cancer “cures”), or for overtopping the head of the hapless non-scientist.

As you recall from Cancer 101, cancer is a proliferation of abnormal cells. This fact alone, that the cells are actively dividing, gives us a target for therapy.

Cells go through particular phases in their lifetimes, but these phases aren’t as simple as “birth, growth, death”. The life of a cell is roughly divided into the cell cycle, during which the cell is preparing for and conducting cell division, and the G0 (G sub zero, or G-naught) phase, where the cell simply goes about all of it’s non-reproductive business, such as structural support and protein production. Normal tissue has a fairly balanced growth fraction, that is the number of cells dividing is roughly equal to the number of cells being lost (to normal programmed cell death and other normal attrition). Cancerous tumors have a higher growth fraction than normal tissue, that is the number of cells in cycle is higher than the number of cells being lost (to programmed cell death, etc.).

The next fact about the biology of cancer is that this growth fraction decreases very quickly as cancers approach detectable size. At that point, cells deeper in the tumor begin to lose their blood and nutrient supply and leave the cell cycle for G0 or death. The dynamics of cancer growth is described by some rather complex (to me) mathematics, but the basic idea is that tumors tend to grow following a Gompertizian curve, that is when they are small they grow exponentially, but as their size increases, growth falls off. For growth fraction to decrease, cells must leave the cell cycle and enter G0 phase, so older, bigger tumors have more cells in G0. This is not true of all cancers, but the concept is important for this reason:

G0 cells are not susceptible to chemotherapy agents.

This is why chemotherapy, which kills cells “in cycle”, is rarely curative. Cancer therapy involves combinations of the many available modalities. Surgery, chemotherapy, radiation therapy, hormonal, immunologic, biologic, targeted, and other therapies can all be combined based on the particular cancer.

Let’s take the example of breast cancer. By the time they are detected, most breast cancers have a fairly low growth fraction, meaning that most of the cancer cells in the primary tumor are not susceptible to chemotherapy. Surgery is the usual initial treatment. After the tumor is removed, depending on the size and whether or not there is evidence of spread, additional treatment can be given. In removing a breast tumor, the goal is to remove as much of the mass as possible, with an edge or margin that is completely clear of cancer cells. This doesn’t mean that there are no cancer cells at all left, but the bulk of the tumor is gone.

Removing the tumor surgically has the advantage of “debulking” the disease, that is any remaining cells are once again part of a smaller tumor mass (a mass which is likely to be microscopic, perhaps only a few cells). As you recall, smaller tumors have higher growth fractions, that is fewer cells in G0 phase, and more in cell cycle. As you might imagine, this means that the tumor can grow back, but it also means that the tumor is now more sensitive to radiation and chemotherapy. In small breast cancers, radiation is delivered to the tumor bed with the goal of killing any stray cancer cells. If the tumor was large, or there is evidence of spread to local lymph nodes, chemotherapy is given by vein so that it reaches the cancer cells wherever they may be.

In addition, certain clever hormonal and biologic therapies can be used in some breast cancers. Some breast cancers have hormone receptors, which, when exposed to estrogen or progesterone, encourage their growth. The drug tamoxifen binds estrogen receptors, preventing the hormone from encouraging cancer cells to divide. (This has the effect of pushing the cell into G0, making it unreachable by chemotherapy, but clinical trials have shown it to be effective in preventing breast cancer recurrences.)

Some breast cancers have a mutation known as HER2/neu, which allows breast cancer cells to keep dividing. A unique biologic agent was designed to block this receptor, causing the cell to remain stuck in part of the cell cycle.

The treatment of cancer is a fascinating and rapidly changing field. New discoveries in biology fuel new discoveries in medicine and in pharmacology, creating a wonderful creative synergy. Cancer is still the second-leading cause of death in the U.S., but there is far more hope than despair in the field. The diagnosis, while life-changing, is only the beginning.

(Note to friend: sorry for not mentioning angiogenesis inhibitors, but I really ran on too much already.)