A friend of mine recently posed some important and insightful questions about cancer.
I provided answers as a molecular biologist and cancer patient, seeking to be clear and as simple as possible.
I hope these good questions and my answers might be helpful, especially to new cancer patients and their family members.
Remember – these answers are not meant to substitute for the advice of a skilled medical doctor familiar with a particular patient.
1 What is cancer and why does it happen?
“Cancer “ describes illnesses where one of the trillions of cells in the body becomes confused and starts to divide out of control. Each cell has a very complicated set of machinery, and the main set of instructions in the cell DNA has more than 20,000 different gene “recipes” or instructions for building all the tiny machines in the cell. We inherit one set of instructions from mom and a second set from dad. The two sets are slightly different, which is why mom and dad looked different from each other and why we look different from each of them. Errors can occur in these gene recipes. Some errors are inherited from our parents, but new errors in the DNA recipes can occur by accident or because of certain exposures in our environment (like cigarette smoke or sunlight) that damage the gene recipes in DNA. Some gene recipe errors confuse cells into dividing to form new cells. Cell division is a very good thing when we are growing up, but uncontrolled cell division can kill us if the growing cells (a “tumor”) spread and damage the rest of the body. Improper cell division that is slow and does not spread is called “benign.” A wart is a kind of uncontrolled cell division that is benign and can be cured by removal. On the other hand, “cancer” refers to uncontrolled dividing cells that spread within the body and damage it. “Malignant cancer” refers to cancer that is in that process of spreading, where control is harder. The weird thing about cancer is that it is part of our own body growing out of control. That makes it a hard problem to solve compared to an infection by a germ, because many treatments that kill the cancer have the potential to damage our normal cells too.
2 How many different types of cancers are there?
Every different kind of human cell has the potential to become confused and grow out of control. Because there are hundreds of different kinds of cells in the body, there are literally hundreds of different kinds of cancer, depending on what kind of cell is growing out of control. Even more common cancers like breast cancer and colon cancer and ovarian cancer and lung cancer actually occur in different types because there are more than one kind of cell in each of these organs. Cancers are usually named for the kind of cell that is confused, and sometimes for the specific source of the confusion. For example, there are many different kinds of blood cancers including lymphomas and leukemias because there are many different kinds of cells in the blood. Because cells are so complicated, there are many different kinds of errors in the gene recipes that might confuse them. GIST (gastrointestinal stromal tumor) is caused when one of a special kind of cell called the “interstitial cell of Cajal” becomes confused and grows out of control. Even for GIST, there are different kinds of gene recipe mistakes that can confuse these cells into growing out of control. Depending on the source of the confusion, different treatments may be indicated. A common analogy is to think of a tiny, invisibly small cell as if it were a tiny car that needs to drive safely. Imagine all the mistakes in a car that could make it unsafe. Imagine if an error is present in the machinery of the brakes so the car can’t stop, or if the gas pedal is broken and stays pressed all the time. That is like cancer. Many other errors might simply prevent the car from running, and those errors would not cause cancer.
3 What does it mean when someone is predisposed to cancer? Why does the risk factor increase?
Errors in the 20,000 gene recipes in the DNA of each cell can arise in different ways. Some errors are pure accidents of DNA copying by the cell machinery. Some errors are caused by our environment, like cigarette smoke or sunlight or radon gas from the earth. Those we can work to avoid by our behavior (stop smoking, wear sunscreen, get our homes checked for radon gas if we live in a part of the country where that is an issue). Some gene recipe errors are inherited from mom or dad. Each parent gives us one complete set of 20,000 gene instructions when we are formed from their single egg and sperm. That way we have two copies of each recipe, and the two versions (spellings of the recipe) from mom and dad are usually slightly different. This is a good thing, and it makes life interesting. Usually if there is a problem with one recipe inherited from one parent, the other copy of the recipe acts like a back-up! Very cool! Sometimes, however, both versions of a recipe happen to have errors, so neither can be a good back-up for the other. In other cases, the one good recipe in a cell can be damaged or lost, and then the only remaining recipes is a broken one. Now that cell has no good copy of the proper recipe and it can become confused. Some people carry damaged recipes that they have inherited. Their cells are still fine with the back-up, but the person has a cancer risk because if the remaining good recipe in a cell is accidentally lost or damaged, there is no remaining back-up and the confused cell starts to divide out of control. It is very important to remember that inherited cancer risk is nobody’s fault. It is also important to know that doctors are now better and better at checking our DNA (from a small blood sample or even cheek cells work fine for this since every cell in the body has the same collection of all the gene recipes) to look for evidence of which gene spelling variations we inherited. Doctors now know some of the most common problems. If we carry one of these, there is a chance that a cell in our body could lose the remaining good copy of the recipe and cancer could start. If we are one of these carriers, doctors may suggest that we are checked for cancer more often, so it might be caught early before it spreads. This really does save lives!
4 What if someone has no known family history of cancer yet they still develop cancer….why does this occur?
Since cancer is about cells being confused by damaged gene recipes, that damage can happen different ways. I might inherit one damaged recipe that can cause problems with no other damage. More often, I might inherit a damaged recipe that causes a problem only if the remaining undamaged recipe is damaged or lost in some cell during my life. However, gene recipes can be damaged even when only good and correct copies had been inherited. This is because the process of copying all 20,000 gene recipes has to happen every time a cell divides. The process is very complicated. Luckily, cells are extremely careful about this and the trillions of cells in the body seldom make errors. However, with so many cells, and so much gene copying, some mistakes are going to happen. If the error is in the wrong place and wrong time, the cell is confused and begins to grow out of control…the first step of cancer even when neither mom nor dad passed along any errors. As we have mentioned, some gene errors are purely random accidents where nothing could be done to prevent them. However, we know that common lifestyle choices can cause gene errors and these errors can be reduced by changing behavior. The two most obvious cases are smoking and sun exposure.
5 How does chemotherapy differ from targeted drug therapy?
“Chemotherapy” really just means “therapy with a chemical.” Because all drugs are really kinds of chemicals, any therapy with a drug is a kind of chemotherapy. However, cancer doctors often speak about chemotherapy as meaning the traditional approach to slow down cancer with drugs that kill cancer cells faster than they kill normal cells. This approach has saved millions of lives, so chemotherapy can be very successful. Many chemotherapies have been improved to have fewer side effects and problems. These improvements are always continuing. Doctors now often refer to “targeted drug therapies” to describe newer drugs that are designed based in the particular confusion in a tumor cell. Rather than just trying to kill the cell because it is dividing out of control, the drug is designed to attack the particular problem. Here is an analogy. Let’s say you are a police department trying to save lives by preventing criminals from speeding over 75 miles per hour as they flee from crime scenes. This might be a good idea. How to do it? One way is to use police helicopters and radar systems to identify every single vehicle (car, truck, bus, train) going faster than 75 mile per hour and assume it is a criminal fleeing a crime and shoot out their tires to get them to stop. If we had enough police and technology, this would indeed solve the problem of criminals speeding away from crime scenes. Good, right? But, what would be the unintended side effects? We might destroy all innocent emergency vehicles driving fast for other good reasons, and trains that are supposed to go fast, and trucks on interstate highways…there are lots of unintended consequences to that approach. This is a little bit like a general chemotherapy. It may be necessary to save life, but it is a “generic” solution to the problem, with side effects. Doctors hope that targeted therapies might be smarter…like only chasing vehicles with license numbers associated with a crime scene, and maybe turning off their engines by remote control technologies rather than shooting their tires. Seem like science fiction? Hopefully more and more cancer drugs will work this way in the future. This is how Gleevec works for certain kinds of GIST!
6 Why are some cancers harder to treat than others?
Cancer cells are cells growing out of control because they have gene errors that cause them to be confused. Different gene errors cause different kinds of confusion. Cells confused so badly that they grow and divide very fast can be very hard to treat. On the other hand some slow cancers are also tricky because the confused cells aren’t that different from normal cells. Imagine in the previous analogy if the criminals escaping from crime scenes are only driving at 69 miles per hour rather than 75? Will we even be able to distinguish those getaway cars from normal drivers? [OK, having lived in Los Angeles, I know these particular speed numbers wouldn't make sense in California!] Another very important thing to understand about cancer cells is that they change. The original confused gene recipe that started a cancer cell growing out of control is passed to the new cancer cells every time that cell divides. BUT, the many, many, many dividing cells also have new chances for making copying mistakes of their own. That means that new gene recipe errors can crop up in the descendants of the original cells. Cancer tumors can have billions and billions of cells, so, unfortunately, many new chances for new gene recipe errors to occur by accident. Every new error has a chance of confusing cells in new ways. If there are a mixture of cancer cells with different errors starting to live together in the tumor, if a new drug is introduced by a doctor, some cells may respond to the drug and die, as desired. However, some of the cells could have gene recipe errors that cause them not to die in the presence of the drug. These cells will keep dividing and the tumor will keep growing because the surviving cells take over. It is important to know that the tumor isn’t “trying” to escape the drug therapy. The tumor doesn’t know anything about drugs – it is just a confused part of your own body. It is just that with so many cells, there will always be some variations with different gene recipe errors, and these different cells may be able to grow when a drug stops all the others. This idea that tumors have different cells with ever-changing gene recipe mistakes means that tumors evolve (a perfect example of the theory of evolution with survival of the fastest-growing cells).
7 What is the difference between chronic illness vs acute illness?
A chronic illness lasts a long time and may persist for the entire life of the patient, being managed perhaps without being cured. Diabetes is a good example. Though, sadly, too many people still die from diabetes and its complications, more and more get care so they can manage their diabetes without it ever being cured. An acute illness refers to an illness that lasts a short time and is either cured or kills the patient. More and more acute illnesses can be treated and cured by modern medicine, so the patient completely recovers and is like new again. We all wish that cancers can be acute illnesses where patients are completely cured after a short time and go back to living normally. I actually have a different dream. I would like to dream that more cancers will be chronic illnesses like diabetes, so that with good drugs and strategies we learn to live with our cancer rather than die from it. I have been blessed to have lived with my SDHB-deficient familial paraganglioma cancer for more than 45 years. Sometimes it has not been a picnic, but it most of the time I don’t need to think about my cancer at all. It is also very important to say something else at this point: from the moment we are conceived, we each are on a path toward death. That is what it means to be a human. It is important to embrace that reality rather than denying it. You might say that our purpose in life is to come to terms with how to make this short life beautiful, and to consider how to learn if there is more beyond this time and space.
8 What can we hope to see from cancer research and development in the next 25 years? 50 years?
The very best things we can learn to do are to 1) prevent more cancers from even starting, and 2) learn to catch more and more cancers early so they are small, have not spread, and can be cured by a small operation to remove the confused cells. We could save a massive amount of cancer suffering very quickly if we could simply convince people to stop smoking and to use sunscreen. Those two steps alone would save thousands of lives and billions of dollars every year. No fancy drugs or new kinds of surgery is required for either. Other cancers can be prevented by simply eating and drinking moderately. So prevention is the simplest, cheapest, and best solution for the future. Because the gene recipes in cells can be damaged throughout our lives, the older we are, the greater the chance of confused cells. There is no escaping that. This is why the next area for improvement is detecting cancer early so it can be cured. Simple life-saving examples are skin checks, breast self-exams, pap smears, and colonoscopies to check the lower intestines for small tumors. Removing such small tumors can completely cure them, whereas larger colon tumors can spread and kill. In the future we will learn to do more and cheaper tests (like the new colon cancer tests that can be done by collecting a stool sample at home and mailing it in to the lab). Over the coming decades I think the biggest reduction of cancer suffering will therefore come from better prevention and better early detection. Because cancer will also always be a disease of aging, no matter how much prevention or early detection, we will need to keep understanding gene recipes and all the ways they can be damaged and all the kinds of cell confusion that can result. That will be a lot of work because many of the 20,000 gene recipes can cause different kinds of confusion if damaged in different ways. We molecular biologists will be busy, and plenty of government funding will be needed for years to come to help develop new smarter and safer drugs that work specially for certain kinds of cancer. A goal will be to find solutions that are less expensive and more accessible as well. Some solutions will be about helping the body help fight off the cancer itself. Some solutions will involve learning about the details of the cell confusion so we can imagine ways to take advantage of it. My own dream is that some cancers will turn out to result from unusual kinds of confusion that may reveal interesting and unusual kinds of drug treatments that are safe and inexpensive!
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