ORIGINALLY PUBLISHED:
1 March 2022
What is epigenetics? How cells modify DNA and RNA
Each of the billions of cells in a person's body has the same DNA blueprint and epigenetics is the process that controls which genes are expressed, giving rise to many different cell types.1 If DNA is the raw code of a genome, epigenetics is how the code 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 Studying the modification of gene expression, rather than the genome itself, gives us a deeper understanding of why these modifications occur, and how to exploit them for drug development.2
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 and RNA in the nucleus.3,11 However, this compact structure means that DNA is inaccessible to the cellular machinery that is required for gene expression.4 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.4 Proteins can also regulate gene expression by modifying DNA and RNA directly.1 Together these epigenetic mechanisms tell a cell which genes to switch on and off throughout a cell’s lifespan, and when. When these mechanisms malfunction, however, they can change the way a cell behaves and can even lead to cancer. 4,12
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.5 As one of six 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 hope to pioneer new ways to attack cancer by modulating gene expression.
Dysregulation of epigenetic processes can result in disease initiation and is a hallmark of cancer.6 By hijacking these processes, cancer can reprogramme a cell’s gene expression profile to favour survival, contributing to its evolution and driving resistance to treatments.6 However, this also creates a tumour-specific vulnerability that can be exploited therapeutically - from cancer detection and targeting to reprogramming immune cells and tackling resistance. 6,7 By studying how these epigenetic malfunctions lead to cancer, we can also develop cancer therapies to target those changes.
Expanding our cancer-fighting toolkit
We are deciphering cancer’s epigenome at the cellular level using cutting edge technologies like multi-omics to generate new insights into the role of epigenetic dysregulation and chromatin remodeling in cancer.8
Deeper understanding of epigenetic changes, particularly changes that occur as a disease begins, could improve our ability to detect cancer with potential to identify and treat cancer in earlier stages.5 By exploring new ways to classify tumours we hope to identify more patient segments to help develop the next wave of precision medicines with the potential to move us closer to cures.9
Epigenomic sequencing is also driving our understanding of drug resistance. Our aim is to understand how cancer manipulates the epigenetic sequencing to resist treatment which may inform novel approaches to overcome this.9
Epigenetics represents an untapped opportunity in cancer biology for researchers, oncologists and tomorrow’s patients living with cancer,” said Ho Man Chan, Executive Director, Head of Epigenetics, Oncology R&D.
Our aim is to build a portfolio of therapies to target cancer and its vulnerabilities, including inhibitors of key epigenetic processes such as chromatin remodeling and RNA or histone modification. Our ambition is a future where epigenetic therapies are embedded into cancer care to ultimately 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. Our collaboration with Accent Therapeutics explores RNA Modifying Proteins (RMPs) as emerging cancer drug targets. RMPs control translation of RNA into protein and are elevated in some cancers, which supports tumour growth and survival.10 We are also partnering with Proteros to identify novel chemical matters to drug epigenetic enzymes.
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 of transforming 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.
