Project details

Researcher: Dr Anita Grigoriadis

Team: Cancer Bioinformatics Laboratory

Location: Breast Cancer Now Research Unit, King’s College London

The challenge

Triple negative breast cancer is one of the more aggressive forms of the disease and makes up about 15 per cent of diagnoses. Unfortunately, there aren’t many targeted treatments available for triple negative breast cancer. This means that treatment after surgery relies on chemotherapy and radiotherapy, which can have significant side effects.

Triple negative is the name given when breast cancer is HER2 negative and hormone receptor negative. Different types of breast cancer can be triple negative. This makes it challenging to find treatments which work for everyone diagnosed with triple negative disease.

We need new targeted therapies for triple negative breast cancers.

The science behind the project

Dr Anita Grigoriadis and colleagues have recently discovered that a molecule called HORMAD1 is present in more than 60 per cent of triple negative breast cancers. HORMAD1 is normally only found in the male testicles, and the fact it’s in so many triple negative breast cancers is a potentially significant finding. Anita and her team have found that HORMAD1 causes changes in the DNA of the cancer cells.

Anita wants to better understand the impact that HORMAD1 is having in triple negative breast tumours and find treatments to target these cancers. The team is using computers to analyse data from a wide range of sources, to answer questions and reveal new insights.

In this project, Anita and her team are studying data obtained from triple negative breast tumours donated by people in clinical trials, as well as cancer cells in the lab and tumours in mice. They are analysing cancer’s genetic code and information on how active the genes are inside cancer cells.

‘Although treatment works very well for some people with triple negative breast cancer, for many, these treatments are either ineffective, or initially successful only to be followed by the regrowth of the disease, which is resistant to treatments. HORMAD1 is present in over 60% of triple negative breast cancers and causes DNA mutations that help the cancer. We are investigating what HORMAD1 does to the DNA and how the presence of HORMAD1 affects the immune system. We hope to identify several other key molecules within these HORMAD1-bearing cancers that can be targeted with drugs, and hopefully provide better ways to treat triple negative breast cancer.’ - Dr Anita Grigoriadis

Anita and her team are focusing on two potential roles for HORMAD1:

Looking for patterns of DNA changes caused by HORMAD1

Anita and her colleagues have previously found that HORMAD1 causes changes in the DNA of breast tumours. In this project, they are reading the DNA code from breast tumours to identify patterns of mutations which are specific to cancers with HORMAD1. This may reveal potential weaknesses which could be targeted with drugs, and could lead to new treatments for people with this form of triple negative breast cancer.

Understanding how the immune system responds to breast cancers with HORMAD1

Anita and her team are also investigating how HORMAD1 influences the ability of the immune system to recognise and destroy breast cancer cells. Because HORMAD1 causes changes in the DNA of the cancer cells, the cells may display unusual molecules on the outside. This could be recognised by the immune system.

The team will identify the types of immune cells found in and around breast cancers that make HORMAD1, and how these immune cells respond to the cancer. They will work out whether this makes these cancers more susceptible to immunotherapies – drugs which improve the immune system’s ability to recognise and destroy breast cancer cells.   

What difference will this project make?

HORMAD1 may represent a new weakness in some triple negative breast cancers, a feature which can be used to identify people who may benefit from particular therapies. By using computers to analyse data, Anita and her team will help to understand how triple negative breast cancers with high levels of HORMAD1 could be treated. Working with colleagues who specialise in lab-based science, their research could lead to new treatments for people with triple negative breast cancer. The hope is this will improve their chances of survival and quality of life.

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