Latest updates from the lab
Action Against Cancer funds research carried out by various teams of dedicated scientists at Imperial College London, the University of Sussex and the University of Manchester. Highlights of their work from 2023 are outlined below.
Also in 2023 Action Against Cancer part funded the establishment of the Professor Stebbing Cell and Molecular Biology Laboratory at Anglia Ruskin University Cambridge.
Cancer stem cells
Action Against Cancer is funding an innovative research project at Imperial College London examining the diversity within cancer cells, and how this can be incorporated into 3D models to better understand how tumours behave in the body. This includes looking at how cancer evolves, how different cancer cells compete with each other, how they develop and spread, and how drugs can be used to target tumour growth and the surrounding environment.
The team has developed a powerful genetic system that allows them to manipulate the genes in cancer cells, as well as models that closely mimic the conditions found in the human body. They have made significant progress related to the identification of the presence of certain cells determining whether cancer has the potential to invade other tissues. They have developed a tool that can predict the correct stage of the disease with a high level of accuracy.
The work aims to uncover new insights into the complex nature of cancer and how it can be targeted and treated more effectively. By understanding the genetic and behavioural diversity of cancer cells, the intention is to improve the ability to predict and develop therapies that are tailored to the specific characteristics of each patient's tumour.
Developing a new drug - A totally new approach to therapy
The team at the University of Sussex (shown right) working on a pioneering drug discovery project is continuing to optimize LMTK3 inhibitors. This includes clarifying the mechanism for action of the drug compounds and testing how specifically and effectively they work to reduce tumour growth.
In addition, the team has generated preliminary data demonstrating a contribution of LMTK3 in the behaviour of immune cells in certain cancer types. It appears that cancer cells overexpressing LMTK3 affect the ability of immune cells to infiltrate and ultimately destroy the cancer cells. This is a further indication of the cancer causing function of LMTK3, in this case ‘indirectly’ by affecting the surrounding tumour microenvironment and its participation in tumour growth.
LMTK3 inhibitors are expected to be able to overcome treatment resistance, offering unprecedented hope for enormous numbers of cancer patients.
Triple negative breast cancer is the most aggressive subtype, metastasising more effectively than other breast cancers. Currently there are no targeted therapies approved for this disease, and it can only be treated with chemotherapy. This means that treatment is often ineffective and causes excessive toxicity and side effects for the patients.
Action Against Cancer is funding a team to identify new therapies using tiny molecules called microRNAs to target triple negative breast cancer. There are advantages to using microRNAs for drug development, including the fact that virtually all of them can be inhibited therapeutically.
The team have used genome editing technology to identify novel microRNAs important for the growth of triple negative breast cancer in order to develop a new drug. Their focus is now to study the molecules further and to perform pre-clinical trials.
A team supported by Action Against Cancer is examining the role that modifications to DNA play in the development of breast cancer. Such modifications can affect how genes are turned on or off, and are found to be disrupted in many cancers.
By using special reagents and microscopy to study tissues from several breast cancer patients, the team has discovered that the levels of a specific modification are localised to specific areas inside the cells where RNA is commonly found. Additionally, they discovered that the levels of the modification within these regions are much higher in the cancer cells compared to the healthy cells from the same patient (image on right). This is particularly true for tissues from triple negative breast cancer patients, as they lack certain hormone receptors.
Learning that this modification is used by cancer cells to possibly regulate crucial pathways in cancer formation is very important. This research is predicted to identify specific genes or proteins that can be targetted for treatment.
The team's work was published recently in the prestigious journal Nature, more on this here.
Understanding the cancer brain
Certain cancers initially respond to endocrine treatment, however 5-20% of the tumours are intrinsically resistant to the treatment, while 30-40% acquire resistance over a period of many years. Resistance to treatment inevitably results in relapse and cancer spreading in the patient’s body.
A team funded by Action Against Cancer and led by Dr Leandro Castellano at The University of Sussex, is investigating resistance to endocrine treatment. They have discovered and characterised a previously unknown molecule that they have shown represses the activity of one of the most important mediators of resistance to therapy, a protein called Cyclin D1. They are now characterising the elements of the molecule that are responsible for Cyclin D1 repression, which could be used as a drug to treat endocrine resistance in the future.