Early Detection Saves Lives!
What Desiderius Eramus of Rotterdamm famously noted almost 500 years ago is still valid today: “prevention is better than cure”. Although research and medical care has made quantum leaps since then, prevention is still one of the most powerful weapons we have against breast tumours: indeed, due to the growing popularity of mammography screening in the 1980s and 1990s, there was a rapid and uniform increase in breast cancer incidence rates, highlighting the power of such screening and detection methods. Early detection in combination with the reduced use of menopausal hormone therapy led to a significant drop in female breast cancer incidence during the early 2000s.
However, even if population-wide breast cancer screening programs aim to reduce breast cancer mortality through early detection and effective treatments, establishing primary prevention programs for breast cancer remains a great challenge. Nevertheless, efforts to decrease excess body weight and alcohol consumption and to encourage physical activity and breastfeeding may have an impact on stemming the incidence of breast cancer worldwide. But still: when cancer occurs, a cure is the only possible way.
Why Further Research is Essential for Developing New Cures
According to International Agency for Research on Cancer, an estimated 19.3 million new cancer cases occurred in 2020. So there still is a great need to find a cure, and indeed, scientific research has brought about many new treatments and compounds to get the job done. But cancer isn’t a typical, by the book illness – and it is therefore impossible to pinpoint one universal medicine for a cure – every single person is different, meaning that also their tumours can be very different from one to the other.
As with other cancers, breast cancer is a very heterogeneous disease, consisting of different entities affecting the same anatomical organ and originating in the same anatomical structure. Heterogeneity represents the primary challenge in treating breast cancer. Understanding the critical biomarkers as well as their role in carcinogenesis, drug resistance, and their use for diagnosis and therapy is crucial for an effective breast cancer treatment.
But What is Cancer, Exactly?
Our bodies, including the breast, are made of millions of cells. Inside these cells, there is an instruction manual called DNA, which has chapters called genes. Genes tell the cells how to behave by coding for proteins, which are the main actors driving biochemical reactions.
Thanks to simple but precise biochemical reactions arranged in a multitude of networks upon networks (called pathways), cells can create and dismantle structures while sustaining a running metabolism in order to gain energy or undergo cell division (known as mitosis), thus making almost identical copies of themselves.
During mitosis, cells also make a copy of their DNA so that each new cell has the very same instructions. Occasionally, the DNA of a cell can get damaged or mutated. To prevent the duplication of these “abnormal” cells, there are special kill switches that, once induced, allow the abnormal cells to commit suicide.
Sometimes, however, mutations arising in “special genes” known to be involved in the development of cancer (called oncogenes or onco-suppressors) can slip by unnoticed and get passed on to new cells through mitosis. Given enough time, a cancer cell will accumulate more and more errors, overlooked by the immune system and beginning to duplicate uncontrollably, producing more and more mutated cells of its kind which eventually develop into a tumour.
If cancer cells are not found and removed soon enough through surgery, irradiation or medications, they can migrate from their site of origin and invade nearby tissues or even metastasize to distant organs.
When Cancer Cells Create a Favourable Environment in Which to Live
Tumours are not solely created by cancer cells growing independently, unrestrained in their reproduction. Instead, tumour cells have strict interactions with their surroundings, called the tumour microenvironment. This special environment comprises both a cellular compartment (made up of cancer-supporting cells, vascular cells and infiltrating immune cells) and an acellular part, called the extracellular matrix – a three-dimensional network made up mainly of proteins and complex sugars.
The extracellular matrix is an essential element not only in tumours but also in healthy tissues, as it acts like a physical basement for the construction of tissues and organs. But besides acting as a physical scaffold to maintain tissue structure, the extracellular matrix also orchestrates biochemical molecules and signals, thus modulating cell functions and behaviours. In fact, altering the fine balance of the extracellular matrix signal is sufficient enough in the long run to induce breast cancer development and progression.
Hyaluronic Acid is a Major Component of the Extracellular Matrix….and Tumour Microenvironment
One of the most well-known and abundant elements present in the extracellular matrix is hyaluronic acid – yes, the very same molecule that is widely used in cosmetics for filling your wrinkles, plumping your lips and hydrating your skin!
Technically, hyaluronic acid is a glycosaminoglycan – that is, a polysaccharide of amino sugars. In few and simple words, it is a series of sugars arranged in size-variable chains!
Thanks to its hydrophilic characteristics, hyaluronic acid has important structural and mechanical roles, such as providing elasticity in the skin, acting as a lubricant between articulating bones in joints and allowing the stretching of blood vessels in response to mechanical forces. It also aids in the tissue repair process by mediating cell adhesion, differentiation, motility and proliferation.
Even though hyaluronic acid can be beneficial in a lot of different situations, it can also be detrimental when a tumour develops. In fact, a high amount of hyaluronic acid present in the tumour microenvironment normally means that the tumour is highly aggressive and could have the potential to invade surrounding tissues and distant organs.
Then, is Hyaluronic Acid a Good or a Bad Guy?
The answer is: both! But how can hyaluronic acid play at the same time a good and a bad role in our bodies? The answer depends on “pathways”! Apart from its swelling properties, hyaluronic acid can also act as a signalling molecule and participate in specific pathways that are triggered by two major proteins located on the cell surface, called CD44 and RHAMM.
Through binding to these proteins, hyaluronic acid can initiate a cascade of biochemical events that finally lead to the expression of specific genes or the activation of proteins that could be involved in propelling cancer cell growth, division and motility. And depending on the protein which hyaluronic acid binds to and interacts with, the final effect will be different, rendering this molecule either a superhero or a villain.
How Research May Help in Taming the Villain
Since hyaluronic acid is generally involved in helping tumours to become aggressive and grow faster, research (including my own current project) is focused on studying all the molecules that interact with hyaluronic acid and its related pathways. Once we have a better understanding of theses interactions, we can subsequently try to develop specific drugs that could be used to finally get rid of the tumour.
To do that, biologists can perform a plethora of different experiments, involving data mining in online databases, conduct in-vitro experiments analysing the behaviours of cultured cells, or even measure the activation of specific genes and proteins.
The outcome of all these experiments will help us to understand how we can decrease hyaluronic acid synthesis, increase its degradation, or block any of the pathways it activates. This will eventually allow us to develop specific medications to slow down cancer cell growth and make them susceptible to death, putting us one step closer to finding a cure.