ORIGINALLY PUBLISHED:
1 March 2022
What is epigenetics? How cells modify DNA and RNA
While each of the billions of cells in a person's body has the same DNA blueprint, epigenetics is the process that controls which genes are expressed, giving rise to hundreds of different cell types.1 If DNA is the raw code of a genome then epigenetics is how the ‘software’ runs when enter is pressed on the keyboard.
Cancer biologists have long known that gene expression is different in different cells. Epigenetics are the reason one type of cell looks and acts differently from another.1,2 Studying the software of gene expression, rather than the genome itself, gives us a deeper understanding of why epigenetic modifications occur, and how to exploit them for drug development.3
Inside every cell is approximately two metres of DNA that is wound around histone proteins and packaged into chromatin, providing an efficient way to organise DNA in the nucleus.4,5 However, this compact structure means that DNA is inaccessible to the cellular machinery that is required for gene expression.6 To overcome this, epigenetic protein complexes known as ‘writers’ add chemical modifications to histones to promote chromatin remodelling. This switches genes on, while ‘erasers’ remove these marks and switch genes off.3 Proteins can also regulate gene expression by modifying DNA and RNA directly.1,2 Together these epigenetic mechanisms tell a cell which gene expression programmes to switch on and off throughout a cell’s lifespan, and when. When the software malfunctions, however, it can change the way a cell behaves and can even lead to cancer.5
Discover more about the role of epigenetic regulation in cancer and how deepening our understanding of the process may lead to the development of new therapeutic approaches in this video:
Entering the epigenetic revolution in cancer treatment
Advances in cancer biology over the last decade have led to a number of emerging fields, including the exploration of epigenetics-based therapies.7 Dysregulation of epigenetic processes is one of the hallmarks of cancer.8 By studying how these epigenetic malfunctions lead to cancer, we can also develop cancer therapies to target those changes. As one of the scientific platforms we’re building across oncology, we are investing in technology and expertise to better understand the role of epigenetics in disease. With this, we are pioneering new ways to attack cancer and address unmet medical needs by targeting proteins involved in epigenetic regulation, like PRMT5 (protein arginine methyltransferase 5).9
Expanding our cancer-fighting toolkit
We are deciphering cancer’s epigenome using cutting edge technologies like multi-omics to generate new insights into the role of epigenetic dysregulation and chromatin remodelling in cancer.10
Deeper understanding of epigenetic changes, particularly changes that occur as a disease evolves, could improve our ability to detect cancer with potential to identify and treat cancer in earlier stages.11 By exploring new ways to classify tumours we hope to more finely define patient segments which in turn will help to develop the next wave of precision medicines with the potential to move us closer to cures.
Epigenomic sequencing is also driving our understanding of drug resistance.11 Our aim is to understand how cancer manipulates the epigenomes to resist treatment which may inform novel approaches to overcome this. A deeper understanding of the cancer epigenomes will be of great value in the development, testing and advancement of novel drug combination regimens when an epigenetic therapy is used in combination with other modalities.3
Our aim is to build a portfolio of therapies to target cancer and its vulnerabilities, including inhibitors of key epigenetic processes such as chromatin remodelling and RNA or histone modification. Our ambition is a future where epigenetic therapies are embedded into cancer care to potentially improve patient outcomes.
We know that great science doesn’t happen in isolation, so we are expanding expertise and capabilities by partnering with experts in the field, such as with Proteros, to identify novel chemical matters to drug epigenetic enzymes.12
Cancer Research and Epigenetics at AstraZeneca
The multidisciplinary epigenetics team is part of our Oncology Research and Development organisation, a dynamic environment where people are challenged to think big and act boldly.
Driven by science, our researchers are at one of the most exciting crossroads in oncology. We are building a world-class team to discover and develop new cancer therapies with the ambition improving patients’ lives. Epigenetics is on the cutting edge of cancer research, and we welcome collaboration among all disease expertise and platforms to help drive this wave of innovation.
