Mark Hoofnagle has a MD and PhD in physiology from the University of Virginia, and is now a general surgery resident. His interest in denialism concerns the use of denialist tactics to confuse public understanding of scientific knowledge.
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.)
Medicine & Health
Comments
Wow-- another great post on cancer and its treatments! This is the most straightforward reason I've heard for why surgery really ought to be followed up by chemo/radiation. Thanks! :)
Posted by: The Perky Skeptic | September 24, 2008 7:31 PM
Thanks a lot for that very straightforward explanation.
Di
Posted by: Di | September 24, 2008 8:23 PM
New discoveries in biology, for example, HB-19 to discourage angiogenesis, also CXCL4.... Understanding how Erythropoietin's role in cancer recurrence is also something that is fairly interesting.
Great post, though, it's difficult to condense such a complicated group of diseases into a relatively basic introduction.
Posted by: Jared | September 25, 2008 12:27 AM
If chemo is attacking a tumor and manages to kill off all (in a perfect world) the active cells leaving only the G0 cells, are these cells dead dead or can they lead to more tumors in the future?
Posted by: the izz | September 25, 2008 12:58 AM
I enjoyed this series of posts. Thanks.
Posted by: Danimal | September 25, 2008 6:33 AM
Great post! Cancer cells are real spooky creatures. I suggest doctors just send in some micro-robots there to shoot them all down.
Posted by: Fred | September 25, 2008 7:37 AM
I'm with fred on this one, micro-robots FTW! Great post, it's nice to have these things explained in a way non-medical people can understand.
Posted by: Ramel | September 25, 2008 8:01 AM
Great post. Having been diagnosed with cancer 4 years ago, I wondered why doctors would go into this field, which might be quite depressing. After all, though there is progress, there are still a good many fatal cancers. My experience is that
(a) they certainly get to do interesting medicine, sometimes a bit on the heroic side, and I assume that there is some thrill here - the doctors get to make decisions that really count
(b) there is indeed much more hope than is generally thought.
Any patient who feels so inclined should learn about cancer mechanisms. Any member of family, friend or colleague of a cancer patient should also - so this means all of us. This knowledge can give psychological strength to bear a disease, or to relate to the persons who have this disease. The significance of statistics, as exemplified by the wonderful paper of Stephen Jay Gould "The Median is not the Mean" can also strengthen and help through bad times.
Keep up with this kind of post, I love them.
Posted by: Michelle Schatzman | September 25, 2008 8:32 AM
I would imagine, based on my lack of knowledge, that angiogenesis inhibition is deserving of its own post.
Posted by: The Chemist | September 25, 2008 8:50 AM
Yes, and I'm just the person to not do it...i do happen to know a few experts, however.
As to the earlier question...cells in G-naught can re-enter the cell cycle and become new tumors.
Posted by: PalMD
| September 25, 2008 8:56 AM
To me, "sciency" is to science as "truthy" is to truth.
Posted by: D. C. Sessions | September 25, 2008 1:34 PM
Michelle, I think you mean "The Median is Not the Message" - http://www.cancerguide.org/median_not_msg.html - which is an excellent essay. I read it in introductory statistics and it was my first exposure to Gould.
Posted by: Natalie | September 25, 2008 5:38 PM
"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."
Sneaky tactic ... force them into a period of rapid growth so you can kill them more effectively.
Posted by: Tsu Dho Nimh | September 25, 2008 8:36 PM
Maybe throw in a little about the difference between hyperplasia and cancer.
Posted by: gillt | September 25, 2008 9:35 PM
Angiogenesis isn't really all that complicated (I don't think). It's all about the tumor getting endothelial cells to migrate into the mass to branch out and form new blood vessels. Lots of factors contribute, but that's the ultimate effect. Tumor grows, needs oxygen and nutrients, secretes FGF and VEGF, endothelial cell migration (ECM), new vessels form, tumor continues to grow; all the while "requesting" new vessel formation. I have a few posts on that on my old blog I need to move to my new one; angiogenesis got my interest when I was working with copperheads. One of the venom proteins targets αvβ3, which is implicated in ECM... I feel that I'm rambling.
Posted by: Jared | September 26, 2008 1:09 AM
dear SIr/Madam
what is your opinion about this blog ,http://bigbulletforcancer.blogspot.com/
it says that there is one bullet for metastase of cancer only in 2 weeks treatment and the cost only 300$
regards
jasmin
Posted by: jasmin | October 7, 2008 5:37 AM