This week’s question comes from Jeremy, who asks, “Is a universal cure for cancer possible and, if so, by what mechanism would it most likely operate?”
This is a question that, no doubt, weighs heavily on the minds of thousands of cancer researchers and physicians across the world. As one might imagine, this is a huge topic with a tremendously wide and varied number of potential answers. I wouldn’t dream of doing the topic the injustice of attempting to lay out even a potential cure for cancer. People much smarter than I have spent their entire professional careers on the topic and we are still not quite there yet. In this article, I will address, instead, what cancer is, how it happens, and what we do to fight it. In the process, it is my goal to provide you, the reader, with the knowledge necessary to understand the basics of cancer biology, genetics, and medical treatments. I also hope to shed some light on potential answers to the question as well. Sorry in advance for this one being long, but such an important topic demands a detailed answer.
No discussion of cancer can start without an understanding of what cancer is and how we get it in the first place. Cancer, in its broadest definition, is a cell that has mutated to allow unrestricted growth and possesses the ability to invade and metastasize to other tissues. There are hundreds of different types of cancers, corresponding to just about every type of tissue in the body. Each has a different characteristic, treatment protocol, and prognosis. However, they all share the elements present in that definition. Let’s discuss a few of the key elements in more detail.
- Mutation: Normal cells become cancerous through a mutation of their genes, often in those that regulate the cell life cycle. These genes are collectively known as “oncogenes” and can be thought of as explosives without a detonator. In other words, these genes aren’t causing any issues until some sort of outside element, like UV light, chemicals, or viral infection, mutates them. These are collectively known as “carcinogens” (“carcino”- cancer, “genic”- to create). Once these oncogenes are triggered, the cells can lose control of its ability to control division and start proliferating unchecked. The cell itself is supposed to undergo a process known as apoptosis (programmed cell death) when its DNA becomes too damaged, but if the damage knocks out the right oncogenes the cell can avoid destroying itself. To be clear, multiple key mutations are necessary to cause cancer, but wholesale damage by carcinogen activity can, over time, cause these mutations to accumulate.
- Unrestricted growth: It is pretty obvious that the body’s cells are not meant to live forever. However, immortality is exactly what cells gain when they become cancerous. Cancer cells undergo a variety of changes that allow them to not only divide indefinitely but also live and grow indefinitely. We already broached the first element, which is the elimination of apoptosis. Second, cancer cells activate enzymes not normally present in mature cells to protect their DNA from further degradation. Cancer cells divide quickly and often, which would under normal circumstances cause a rapid degeneration of the DNA after a few generations (which, again, leads to apoptosis). To prevent this from happening, cancer cells utilize telomerase to ensure the integrity of the chromosomes indefinitely. Telomerase does this by ensuring the length of the DNA “caps” that exist at the end of DNA strands, known as telomeres. Telomeres prevent the catastrophic loss of coding DNA at the terminal ends but in doing so take the brunt of punishment, shortening over time in healthy cells. Cancer cells avoid this shortening, and thus are able to continue to divide unhindered. This unhindered division is what causes the creation of tumors. Cancer cells also generate their own growth factors (chemicals that signal cells to divide), are insensitive to anti-growth factors (which prevent cell division), and can create their own blood supply (by a process known as “angiogenesis”). So not only are cancer cells genetically immortal, they also control their own reproduction and grow their own blood supply.
- Invasion and metastasis: Until now, we have not differentiated between benign and cancerous tumor formation. Benign tumors also can grow uncontrolled, though often at a slower rate, and are also caused by abnormal cells. However, invasion and metastasis are what truly change the game and make cancer so dangerous. Invasion refers to the ability of a tumor to spread to other local issues. An excellent metaphor for invasion is a fire: it spreads by setting fire to its local surroundings. A benign tumor can only exist in its original tissue and simply just grows larger from there. The level of invasiveness into local tissues is one way cancer severity is graded. Directly related invasion, metastasis is a cancer’s ability to travel to distant tissues and cause cancer there. Often, this is accomplished by cancerous invasion of blood or lymphatic vessels, resulting in the release of cells systemically. This level of invasion is normally only accomplished by an advanced cancer, so metastasis can be thought of as one of the final stages of cancer development. This is not necessarily true for all types of cancers depending on where they are, but it is a good general guide. The migratory cancer cells often find home in tissues close by, such as bone or other organs. Benign tumors can grow too large for the surroundings and push on neighboring tissues, but only a cancerous tumor can make its way directly into another type of tissue and set up shop there.
So, now that we have a broad understanding of what a cancer is, we should more deeply explore how cancers occur on a cellular level. This will give us a good molecular understanding of the disease and help us better understand the treatment options we will discuss a little later. As I discussed before, DNA damage is primarily responsible for allowing cancers to form. I think that most of us have heard the term “carcinogen” before but don’t necessarily have a clear understanding of how they work save for “they cause cancer.” Carcinogens generally work their magic by disrupting DNA, which can happen in a variety of ways. For example, UV light is carcinogenic because it causes breaks in the DNA strands and photochemical reactions within the DNA (called “pyrimidine dimers” if you’re curious). These breaks and abnormal reactions have to be repaired, and often this repair is not as exact or elegant as we might wish, resulting in a mutation. Over time, UV exposure can cause enough of these damaged segments and mutations that the cell cannot catch up, leading to apoptosis or the formation of cancer. The peeling skin from a sunburn is a result of mass apoptosis from extensive UV damage and photochemical reactions within melanocyte (cells that produce skin pigment) DNA are largely responsible for the dangerous skin cancer melanoma. Carcinogens, then, can be understood to be the detonator to the oncogene’s explosives. They are the environmental factors that alter the DNA. However, outside carcinogens are not the only sources of cancer. Sometimes, the genes themselves create an unfortunate, spontaneous mutation that accomplishes the same goal. This sort of cancer normally arises in metabolically active tissues, such as glands, as high activity levels generate byproducts that can naturally mutate DNA. Rapidly proliferating tissues, like bone marrow, can also have this issue because of the increased possibility of mutation due to the increased number of cell divisions.
But, we obviously walk in the sun, smoke cigarettes, drink alcohol, breathe in all kinds of air pollution, and yet we aren’t all riddled with cancerous tumors. The main reason for this is the immune system. Often, we think of the immune system as simply protecting us from outside invaders. While it does this job very effectively, it also has an entire section devoted just to identifying and destroying rogue cells. It accomplishes this by the major histocompatibility complex (MHC) system, which allows the immune system to identify “self” versus “non-self” cells based on proteins the cell presents on its surface via the MHC system. A type of T cell called a cytotoxic T cell recognizes cells with “non-self” protein presentation and destroys them. Cells known as natural killer cells also perform the same function, but do not require MHC presentation. Generally, these two types of cells destroy cancer cells before they can grow significantly and become invasive by identifying the altered surface proteins they present. The cancer cell also sheds altered proteins, prompting other immune cells to respond and stimulating further cytotoxic T and natural killer cell activity.
Cancers by their very nature are invasive growths, and thus release a host of chemicals and proteins to allow this growth to proceed unhindered. This process is known as “carcinogenesis” and involves many of the elements we established earlier in this article. However, one element we have not yet discussed was the reduction of DNA repair mechanisms within cancerous cells. Combined with rapid replication, this allows cancer cells to mutate at a rapid rate. Thus, if a cancer is not quickly identified and destroyed by the immune system, it can mutate itself rapidly to the point that the immune system either cannot recognize it and/or it is so diverse that it cannot readily mount a response. Thus, cancers that grow are able to do so by evading the immune system until its too late.
Now that we have established the basis for cancer development, we will move on to its treatment. Cancer treatment currently relies on three principle mechanisms of cancer biology: tumor formation, weak DNA repair, and rapid cell proliferation.
- Surgery: Tumors are, at least at their earlier stages, a self-contained body of cancerous cells that can under many circumstances be surgically removed from the body. Many times a tumor can be removed whole, but reduction of tumor size can also be used in conjunction with other treatment methods to treat more dangerous, advanced, and/or invasive tumors.
- Weak DNA repair: Attacking weak DNA repair mechanisms involves use of radiation. Radiation is intended as a focused treatment to a particular area, with the goal of damaging as little healthy tissue as possible. The radiation causes significant DNA damage to the target area, with the goal of causing so much DNA damage in the cancer that it can no longer divide or survive.
- Rapid cell proliferation: Chemotherapy is used to target increased cell reproduction through a variety of mechanisms. Often they target various aspects of mitosis (cell division). Because cancer cells are undergoing mitosis at a much more rapid rate than most of the rest of the body, they are much more susceptible to chemicals that, for example, replace building blocks of DNA, disrupt DNA by bonding to it, interfere with replication enzymes, or destroy the mechanisms that allow for cells and chromosomes to properly divide. Unfortunately, these effects are systemic and can hurt other areas that quickly divide, such as the lining of the gut, hair follicles, and bone marrow.
Because of side effects, all of these therapies can and often are used in conjunction (as necessary) so as to create a multi-focal approach that minimizes the risk present in one particular treatment method. New delivery mechanisms, including implanted irradiated seeds, nanoparticles, and direct tumor chemotherapy, are constantly being developed to increase the effectiveness of treatments while minimizing side effects.
Given all of this information, which really represents just a thin skimming of the facts at hand, can we see a true universal cure for cancer? The answer is likely no, based on our current understanding of cancer biology. Simply, cancers have tremendous diversity in almost every conceivable way. While a particular cancer in two different people may be pretty consistent, two different types of cancer may be strikingly different in almost every way. Adding to that the rapid mutation rate and self-protective mechanisms often found in tumors make the potential avenues endless; just like cancers grow to out-fox the immune system, so too can they outgrow our ability to treat them with the same methods. That is not to say we do not have tremendously effective treatments for certain cancers, which we most certainly do. It simply appears that the link between all cancers that we can regularly and reliably exploit from the outside is not currently known and may not even exist. However, based on our discussion, it seems that the major wild card in this issue is the immune system itself, which has the power to fight cancer on a level we have only begun to explore. This represents a major avenue for research and may hold the key to battling cancer regardless of type.
Hope this helps, Jeremy! Thanks for the question. As always, feel free to submit your own question via the question submission tab at the top of the page.
Till next time,