SHIFTING STRATEGIES

How Science is Adapting to Defeat Cancer

by Sheila Wiebe

Flying cars, free healthcare and limitless communication: for most Western countries, the ambitions of the 21st century have only just started to take shape. Things humans could only dream of in the past are now our self-evident reality. Science eradicated smallpox, found a vaccine for polio, and dying from a cold is no longer a fate an average person has to deal with. With this being said, it is more than obvious to everyone who has spared a look at the cause of death in the past centuries that there is an enemy hiding behind this picturesque paradise of Western medicine. The question remains: why has humankind not yet cured cancer?

The cancer phenomenon

The historical search to find the answer to this question has been, in many ways, symbolic of the way cancer behaves. Even though breakthroughs in cancer research seem to happen quite frequently, they are merely scratching the surface of a bigger problem. We see researchers as our heroes, Hercules fighting an invisible beast, but what if cancer is like the hydra, a serpentine lake monster with countless heads that regrow two just as one gets chopped off?

Sadly, this is exactly the reality we are dealing with when we look at the dynamic of cancer’s properties and the search for a cure. To understand why the countless attempts at putting an end to this fight have failed more or less miserably, one has to look at the exceptional characteristics that make cancer tumours such a uniquely challenging opponent. Or, in other words: let us look at the heads that our medical heroes have to cut off.

The first and most obvious challenge researchers are facing is the sheer range of cancer types. They all indeed share a name, but science describes over 200 diseases under that umbrella term. Although they are all caused by changes in the DNA and spread by uncontrollable cell division (mitosis), each has its quirks and variabilities that create the necessity of treating them separately.

This pattern of variability continues to make things more complicated as one takes a closer look into microscopic structures. As every human’s DNA is unique, our bodies produce different types of proteins depending on our genes. This also applies to cancer DNA: it has an exceptionally high rate of mitosis, producing countless DNA variants that give each cancer cell distinct characteristics. This state of containing diverse elements in a single organism is labelled as heterogeneity. In practice, it impacts not only the affected individuals’ vulnerability to cancer but also their and their tumours’ responses to treatments.

In the lab, treating various tumours - or cutting off these heads of the hydra - leads to an endless cycle of sampling cells, finding out their structure, and developing a treatment that will be obsolete in the unavoidable case that the cells change their integrity. Even in the event in which researchers succeed, another form of variability adds further complexity. Through a trait called clonal heterogeneity, cancer tumours are able to produce mutated sub-clones that differ from the original specimen. These can detach and escape into the circulatory and lymphatic systems of the body. Because of these different types of heterogeneity, only a certain range of cancer cells can be eradicated every time researchers develop a new treatment. The cells with diverging DNA cannot be targeted and therefore remain in a patient’s body. This means that treatment can act as selective pressure, creating a mechanism where only the strongest cancer cells survive. The methods that have been created to act as a remedy unexpectedly have the completely opposite effect of making the cancer more resistant, similar to antibiotic resistance in bacteria.

Besides these properties of multiplication, cancer has additional weapons that make it the invincible hydra we are dealing with. It truly needs them, as it is not only being attacked from the outside, but also from the inside by our immune system. To fight back, cancer has developed strategies to weaken it. Most notably in leukaemia and lymphoma (both types of blood cancer), tumours do this by spreading into the bone marrow, the place where infection-fighting blood cells are produced. Due to this, cancer patients are often more susceptible to illness, making it harder for their bodies to detect and fight other threats.

In addition to this increased vulnerability, the presence of cancer stem cells plays a crucial role in the disease’s persistence. Being the root of cancer’s unstoppable growth, they have an enhanced ability to invade and migrate. Most importantly, they can resist treatments like chemo- and radiotherapy. Even if the whole tumour is eradicated, a single stem cell could seed the growth of a new one. This makes them one of the main targets that researchers aim at when developing treatments, hoping to eradicate the issue at its source.

Evolving treatment strategies

When looking at cancer treatments, surgery is usually considered as one of the most wellknown, but also the most feared at the same time. The spectrum of possible interventions ranges from taking tissue samples and removing suspicious, superficial skin changes to minimally invasive surgical techniques, in which surgical instruments are used through a small incision, all the way to conventional, so-called open surgery. In the latter, parts of an organ or even the entire affected organ as well as neighbouring tissue affected by the tumour can be removed. But recalling the information we now have about our enemy, we can already predict its reaction: By removing one problem, another one arises. Even the most precise and modern technology is, more often than not, unable to remove all cancerous tissue with absolute precision.

The way experts try to tackle the problem of leftover cells is through methods like chemotherapy and radiotherapy. While surgery tries to be as precise as possible, these therapies have only one goal: to kill as many cells as possible. Though it sounds brutal at first, chemoand radiotherapy can help to eradicate leftover cancer cells during or after other treatments because they are designed to kill fast-growing cells. Nevertheless, the concern is not unfounded. If the tumour shows no vulnerability to them, they attack fast-growing healthy cells that are part of the immune system. This way, our most valuable weapons eventually turn into a self-destructive mechanism: where surgery acts like a dagger in the skin of the hydra, chemotherapy infiltrates the whole lake it lives in, poisoning the beast, but most likely also the other living organisms within.

Given the present limitations and challenges with cancer treatment, the question arises if there even is an effective weapon in our repertoire. The good news is that there are new methods with significant potential. As to not lose the fighting spirit that is vital in this never-ending challenge, let us look at the results of more recent research.

A new approach to cancer treatments is using the body’s immune system to fight cancer from the inside. As already established, the immune system identifies dangerous cells and is able to eradicate them in a precise way. The main obstacle here is that cancer cells have the same structure as body cells, which is why the immune system cannot recognise them as a threat. Therefore, the main objective for researchers is to help the immune system recognise cancer cells as malignant.

This is possible in multiple ways: Firstly, we have immunotherapy, where cells that are already sensitised to a certain type of cancer are taken from affected organisms and given to patients to strengthen their immune response. Secondly, there is the possibility of cancer vaccines. Some may be surprised by their existence because most people are used to dealing with vaccines in the context of viruses and infections, but they can be applied in a similar way when treating cancer. Genetic information about a patient’s specific tumour is extracted and analysed to find out its unique features. With this information, the immune system can be stimulated to recognise the cancer cells and attack them.

To make this process even more precise, advanced research uses gene manipulation with a technology called CRISPR-Cas9. With this tool, parts of DNA can be altered, added, or removed altogether. As established, the main obstacle in treating cancer is its growth and variability. CRISPR-cas9 can eliminate precisely these characteristics by modifying the genome of immune cells, which in turn attack parts of cancer DNA.

Gene editing could entirely revolutionise the way we treat cancer, but economic challenges make it hard to substantiate. Even if CRISPR-cas9 is very effective, it involves knowing the genetic makeup of the cells that are being targeted. This process is incredibly expensive, especially because it would need to be repeated numerous times to account for the countless and ever-changing types of cells found in cancer patients. To put it simply, gene editing has a lot of potential for the future, but for now, its complexity makes it way too expensive for it to be profitable for the medical industry.

Obstacles In Clinical Testing

This brings us to another significant challenge in cancer research, one that is less about the cancer itself and more about the methods we use to combat it. In clinical research, most cancer treatments are developed using cultures of cancer cells in laboratories. While we possess critical insights about the fundamental biology of cancer using this method, the nature of a tumour in a petri dish differs largely from the complexity that a specimen in a living organism entails. This phenomenon occurs because cancer cells in organisms adapt to their environment, whereas separated ones do not interact with it at all. Accordingly, cures that seem to be effective on lab-grown cells often do not work in clinical trials with real patients. Even animal trials frequently yield ineffective results. A well-known instance showing the insufficiency of animal testing happened in 2006 when the cancer drug Theralizumab was developed. After being created in a laboratory and tested on multiple different animals to ensure safety and efficacy, it was deemed an effective treatment. Following the first infusion of a minuscule dose, all six human volunteers faced life-threatening conditions involving multiorgan failure. This incident reshaped the way clinical trials are conducted and approved by authorities, but it did not change the fact that, in general, cancer treatments are still developed in animal trials that are insufficient and dangerous for all involved living beings.

Future Perspectives

Looking at the disillusioning reality, what are the measures that need to be implemented to drive meaningful change? First of all, researchers must find experimental systems that match the complexity of the human body. These should be flexible while the cancer moves and changes depending on its environment to prevent immune suppression.

We need to face the reality that, even if it is an uncomfortable fact, cancer can happen to every one of us. All of the mentioned methods are considerably more successful when implemented in its early stages, which is why prevention is still the most effective cure we have against cancer.

While studies about new treatments progress and promising methods are on the horizon, money and time are necessary to extend the research.

However, when we talk about cancer, the term includes 200 different types of diseases, meaning that, as an illness, it will not be solved in its entirety. More realistically, some varieties of cancer could be eradicated individually, taking us one step closer at a time to cure the disease.