Sunday, July 28, 2013

How does cancer treatment work?

"Cancer" is an umbrella term for hundreds of different diseases.  Cancer arises when cells in the body become unable to regulate their division, and grow out of control.  Since cancer can arise from almost any cell in the body, and each of these cells have different characteristics, each different site of cancer (breast, prostate, lung, etc) behaves almost as its own distinct disease.  On top of that, the underlying DNA mutations which give the tumors their malignant traits can also differ.  For example, in breast cancer, tumors can harbor a number of distinct gene mutations (such as estrogen/progesterone receptors or HER-2 receptors).  Each one of these is a different subtype of breast cancer, and has its own prognosis and treatment options.  Some drugs may work on one type, but not on another.

I think that one of the most difficult parts of undergoing cancer treatment is the myriad of options one is presented with.  Will you undergo surgery, chemo, radiation?  What kind of radiation will you get?  Which surgeon will you go to?  How much treatment can you avoid while still giving yourself the best chance at survival?  I can't write an end-all, be-all guide to cancer treatment options.  But I can try to explain what cancer treatment does, the strengths and weaknesses of each type of treatment, and how they work together to extend life.  

Cancer progression and the goals of treatment


To understand what cancer treatment does, we need to understand how cancer progresses.  A tumor is made of cells that grow and divide out of control.  These cells form a mass in the site where they arise (the primary tumor).  The primary tumor will grow and press on nearby tissue, but on its own it is usually not life-threatening.  The danger comes when the tumor spreads to other parts of the body.  

Tumors typically will first spread to nearby lymph nodes, which are organs of the immune system that act as a trap for foreign particles.  If a tumor cell drains into a lymph node, it can start growing into a new mass.  Even more dangerous is when the tumor metastasizes.  If left unchecked, tumors tend to begin invading and degrading nearby tissue.  This can lead to tumor cells entering the blood stream and traveling to distant parts of the body.  Metastases commonly arise in organs with a large blood supply - the brain, liver, or bones.  Tumor cells which land here can form secondary tumors, and are almost always life-threatening. 

In theory, all it takes is a single tumor cell to grow into a new tumor.  As long as there are tumor cells still present and dividing in the body, there is a risk that they can spread.  So, the goal of cancer treatment is to kill or incapacitate every single tumor cell in the body.  Yet the goal of any medical intervention is to improve the patient's quality of life.  Cancer treatment must kill the tumor, but it must also do as little harm to normal tissue as possible.  So every therapy must balance the benefits of treatment with the risks of side effects.

Surgery


The most straightforward way to remove a tumor is to remove it surgically.  A surgeon cuts open the body, goes in, sees where the tumor is, and cuts out everything that can safely be removed.  Surgery is the most effective treatment in almost any site of disease, and is the standard by which other treatments are usually measured.

Surgery is excellent at removing so-called "bulk" disease.  In chemotherapy, drugs can only reach the tumor cells that have blood supply.  In surgery, the entire bulk tumor is removed at once.  Surgery is also a very targeted therapy, since the only tissues affected by surgery are the ones the surgeon cuts into.  Because of this, surgery is excellent at dealing with early-stage cancer that hasn't had a chance to spread or invade nearby tissue.  If the tumor is confined to a well-defined area, then it can be removed.

On the other hand, surgery is very invasive (as anyone who has had surgery can attest).  The surgeon must cut his/her way through the body in order to get to the tumor, and also cut into nearby tissue to find where the tumor has spread.  If tumor cells have invaded nearby nerves or major blood vessels, it may be impossible to remove without doing serious harm to the patient.     

Chemotherapy


Compared to surgery, chemo is known as a systemic treatment.  When the drug is injected into the body, it travels everywhere that blood can reach.  Strangely enough, tumors themselves have very poor blood supplies, and often times chemotherapy cannot treat the entire bulk tumor (surgery is much better in this regard).  But it is good at reaching places where the tumor may have spread.  This is chemo's best aspect - metastatic disease is dangerous, and chemotherapy can reach microscopic cancer outcroppings before they manifest into clinically significant lesions.

Chemo is a bit simpler to understand, since drugs are very familiar to us.  For instance, if you have a bacterial infection, all you need to do is simply take an antibiotic.  But we might not think as often about a drug's mechanism - how we make it do what we want it to.  How does an antibiotic know to kill the bacteria, but not hurt normal tissue?  There needs to be some difference between the normal and abnormal cells that the drug can exploit.  Take penicillin, for example. Some bacterial cells differ from human cells in that they have a cell wall.  Penicillin works by destroying these cell walls.  This action kills bacteria, but since human cells do not have walls, they are unharmed.

The trouble with treating cancer is that a tumor is composed of the same types of cells as the rest of the body.  Your immune system has trouble telling a cancerous cell from a normal one.  Moreover, there are very few chemical distinctions between cancerous cells and normal cells that allow for a drug to act on one but not the other.  One famous scientist likens searching for chemotherapy agents to finding a drug that can kill your left ear while leaving your right ear unhurt.

Let's say you had a forest full of maple and oak trees.  The maples want more sunlight, but the oaks are too tall.  So to alleviate the problem, you go in and chop down every tree over 100 ft high. In general, this accomplishes your task - you remove most of the oaks, and the maples can bask in the sun.  But you also probably chopped down a fair number of the tall maples, and you also missed all the short oaks.  By targeting a trait of the trees which is shared by other species, your "therapy" had unintended consequences.

One of the defining traits of cancer cells is that they divide very rapidly.  So, the first chemo drugs worked by killing cells that undergo cellular division at a high rate.  However, this has the side effect of harming the other cells which are undergoing normal cell division!  Things like hair, bone marrow, or the intestinal lining will suffer damage from this type of drug, and this is the reason why many types chemotherapy are so toxic to the body.  By targeting traits of cancer, the drug also harms normal cells which exhibit these traits.

More modern chemotherapy drugs target traits that are specific to cancer cell genes.  For instance, a lung tumor may be growing quickly because it overexpresses a gene for something called Endothelial Growth Factor Receptor.  This is a receptor that receives signals to grow and divide, and by making thousands of copies, a tumor cell is hyper-sensitized to growth signals (leading to excess growth).  But this is also a weakness - drugs like erlotnib and gefitnib can bind to these receptors and kill the cell.

Radiation Therapy


Radiation therapy is the red-headed stepchild of cancer treatment.  Many people have never heard of it (which is part of the reason why most people scratch their heads when I say I am a "Medical Physicist").  Yet radiation is perhaps the first treatment to definitively cure a sub-type of cancer (Hodgkin's Lymphoma), and remains an integral part of modern cancer therapy.

When ionizing radiation interacts with cells in the body, it knocks millions of electrons out of their atoms.  Chemically, this leaves these ions in a very reactive state (free-radicals), and they cause lots of errant damage to nearby molecules.  If one of these free radicals is near the DNA of a cell, it can break it.

Cells react to DNA damage in several ways.  First off, the cell can simply repair the damage, and go on as normal.  If the damage is not repaired, the cell may die (since DNA encodes for the enzymes and proteins that a cell needs to live).  Or, the cell may detect that its DNA is damaged, and undergo a process called "apoptosis" (cell suicide).  The cell may also enter a state where it is able to live, but is unable to divide (mitotic death).  Any of these things would amount to success, if the goal is to keep a cancer cell from living and dividing.

In order for a cell to repair DNA damage, the repair enzymes must be able to find the damage.  Here's the kicker - if a cell is in the process of dividing, its DNA is bound up tightly into chromosomes.  If the DNA is damaged during division, then it is much harder to repair that damage.  And since cancer cells are undergoing division much more frequently than normal cells, they are very sensitive to radiation (compared to normal tissue).  This is why we use radiation to treat cancer - tumor cells are inherently more sensitive to radiation damage.

Another advantage of radiation therapy is that it is non-invasive.  Using a medical linear accelerator, we can produce a small, focused beam of x-rays.  The patient lays on a movable tabletop, and the accelerator rotates around, delivering radiation from several different angles.  These beams enter the body at different places, and all converge on the tumor.  In this way, the tumor is given as much radiation as possible, and the normal tissue receives a lower dose.

Radiation is very useful for hitting microscopic pieces of the tumor that the surgeons may have missed.  Or, if the surgeons feel that the tumor is inoperable, radiation can be used to treat the bulk disease.  If there are multiple lesions in a nearby place (such as many small lesions in the brain or liver), radiation can be used to treat all of them simultaneously.

Combination Therapy


The reason we use surgery, chemotherapy, and radiotherapy is that they are so effective when used in conjunction with each other.  Surgery removes the original tumor.  Radiation treats the tumor bed, and kills any microscopic spread of the cancerous cells.  Chemotherapy is a systemic treatment that kills any cancer cells that may be working their way around the body, trying to set up new colonies.  Together,  these three treatments will hopefully kill every single tumor cell in the body.  Without radiation, there might be a recurrence in the original tumor site.  Without chemotherapy, there may be metastases.  And without surgery, it may be hard to control the original, bulk tumor.


Each of these therapies also causes harmful side effects.  So when deciding on the best course of treatment, doctors only use as much therapy as is needed.  For instance, early-stage prostate cancer is very unlikely to systematically spread, and is usually confined to the prostate.  So this type of cancer can be treated with only surgery, or local radiation.  In leukemia, the cancer is spread throughout the bloodstream.  So surgery/radiation has little effect, and chemotherapy alone is often the best course of treatment.

Like I said before, this isn't an end-all, be-all guide to cancer therapy.  There are hundreds of different types of cancer, and each one calls for its own specialized course of treatment.  But almost all treatments are going to involve some combination of surgery, radiation, and chemotherapy.

Thursday, February 28, 2013

What ACTUALLY Causes Cancer?

Cell phones.  Microwaves.  Diet soda.  Sugar.  Power lines.  TV screens.

Every day, we are exposed to a laundry list of modern devices and substances.  And I would bet that most of us have wondered what the effects of all those substances are.  The list above is are things that are usually found in news headlines, right before the part that screams "CAUSES CANCER!!"

When you stub your toe, there is no question what the cause was.  But cancer takes years, even decades, to develop.  We carry our cell phones every day, use microwaves to heat our food, and drink our diet sodas at work.  And as humans, we like to attribute things to a cause.  So when someone hears about a diagnosis of brain cancer, it is natural to wonder what really happened over all those years of holding a cell phone to your head.

So, what causes cancer?  There are two ways to answer that question - one way which lends itself to fear mongering, and one way which lends itself to rational public health decisions.  I'll let you guess which one I prefer.

Read more after the break.