Decoding cancer’s epigenetics for next-generation therapies

Advances in oncology over the last decade have led to a number of emerging fields, including the exploration of epigenetics-based therapies.1 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 and pioneer new ways to attack cancer by modulating gene expression.
 

Entering the epigenetic revolution

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.2 If DNA is the raw code of a genome, epigenetics is how the code runs when ‘enter’ is pressed on the keyboard.

Every cell contains 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.3 However, this compact structure means that DNA is inaccessible to the cellular machinery that is required for gene expression.4 To overcome this, protein complexes known as epigenetic ‘writers’ add chemical modifications to histones to promote chromatin remodelling and switch genes on, while ‘erasers’ remove these marks and switch genes off.4 Epigenetic proteins also regulate gene expression by modifying DNA and RNA directly.

Dysregulation of epigenetic processes can result in disease initiation and is a hallmark of cancer.4 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.5 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. 5,6

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 in cancer.7

Deeper understanding of epigenetic changes, particularly those occurring during disease initiation could improve our ability to detect cancer with potential to identify and treat cancer in earlier stages.1 By exploring new ways to classify tumours we hope to identify more patient segments to help us 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. Our aim is to understand how cancer manipulates epigenetics to resist treatment which may inform novel approaches to overcome this.8  

Epigenetics represents an untapped opportunity in cancer biology for researchers, oncologists and tomorrow’s patients living with cancer, Our aim is to build a portfolio of epigenetic 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.

Ho Man Chan Executive Director, Head of Epigenetics, Oncology R&D

We know that great science doesn’t happen in isolation and 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.9 We are also partnering with Proteros to identify novel chemical matters to drug epigenetic enzymes.

Expanding our cancer-fighting toolkit

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 epigenetics 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.


Topic:



You may also like

References

1. Weinhold B. Epigenetics: The science of change. Environ Health Perspect. 2006;114(3): A160–A167.

2. MedlinePlus. What is epigenetics? Available at: https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/. Accessed February 2022.

3. Alberts B, Johnson A, Lewis J, et al. Chromosomal DNA and its packaging in the chromatin fiber. New York Garland Science. 2022.

4. Phillips T, Shaw K. Chromatin remodeling in eukaryotes. Nature Education. 2008;1(1):209

5. Wainwright EN, Scaffidi, P. Epigenetics and cancer stem cells: Unleashing, hijacking, and restricting cellular plasticity. Trends Cancer. 2017;3(5): 372–386.

6. Kaur J, Daoud A, Eblen ST. Targeting chromatic remodeling for cancer therapy. Curr Mol Pharmacol. 2019;12(3):215-229.

7. Pettini F, et al. Multi-omics model applied to cancer genetics. Int J Mol Sci. 2021; 22(11): 5751.

8. Herceg Z, Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol. 2007; 1(1): 26–41.

9. Accent Therapeutics. RNA-modifying proteins. Available at: https://www.accenttx.com/our-scientific-focus/rna-modifying-proteins/. Accessed February 2022.


Veeva ID: Z4-42016
Last Updated: February 2022