Researchers from the University of Birmingham have been awarded project grants to investigate weaknesses in cancers which could lead to new treatments.
The University of Birmingham's Professor Jo Morris and Professor Clare Davies have both received grants from the Medical Research Council, £763,514 and £704,150 respectively, to carry out research into breast, ovarian and lung cancer.
Professor Morris will use the funding for a new study to better understand why some inherited breast and ovarian cancers respond well to treatment, while others do not, and how this could lead to more effective treatment.
Around 5-10% of breast cancers and up to 15% of ovarian cancers are linked to inherited changes in genes called BRCA1 or BRCA2. These genes normally help protect cells from DNA damage. Cancer cells with BRCA gene faults already have a poor repair system. Certain treatments, such as PARP inhibitor drugs, take advantage of this weakness and prevent cancer cells repairing themselves. However, many patients either do not respond to these drugs, or their cancers become resistant over time.
Birmingham researchers will focus on the build-up of small gaps in DNA that occur during cell division. These gaps arise when cells struggle to copy their DNA accurately, which is particularly common in BRCA-mutant cancers. Researchers will investigate how BRCA1 and BRCA2 normally prevent these DNA gaps from forming, and why they fail to do so in some cancers.
By studying these mechanisms in detail, the researchers will aim to identify new vulnerabilities in cancer cells that could be targeted with drugs, either alone or in combination with existing therapies.
This funding will help us answer a long-standing question about how useful these little gaps might be for cancer therapy.
The aim of the study is ultimately to improve how patients are matched to treatments. If specific DNA damage patterns can predict whether a tumour will respond to a particular therapy, doctors could make more informed treatment decisions and avoid ineffective options.
Professor Davies will use the funding for a study investigating lung squamous cell carcinoma (LUSC), one of the most challenging lung cancers to treat. Targeted therapies for this cancer are limited, leaving patients reliant on standard chemotherapies that often fail due to resistance and relapse.
Birmingham researchers will attempt to understand the hidden mechanisms that allow these cancer cells to survive and subsequently identify potential new treatments.
A defining feature of LUSC is a region packed with genes known to support tumour growth. Within this, a new connection has emerged involving PRMT1, an enzyme that modifies proteins. This chemical change can dramatically alter how proteins behave, and in cancer PRMT1 is frequently overactive, driving tumour growth and resistance to treatment.
PRMT1 inhibitors are already used in clinical trials, but the exact pathways through which they support cancer survival remain unclear. It is therefore difficult to identify which patients will benefit most from these drugs or how to combine them effectively with other therapies.
Recent research from Birmingham revealed that PRMT1 becomes especially important when cancer cells face replication stress, a form of DNA damage triggered by rapid, uncontrolled cell division. To survive replication stress, cancer cells rely on specialised repair mechanisms. When this pathway is disrupted, cancer cells become more vulnerable, accumulating DNA damage and causing cell death.
Crucially, cells that depend heavily on this process are also more sensitive to PRMT1 inhibitors, which suggests this could be a potential biomarker for treatment response.
This funding will enable us to fully understand mechanistically how PRMT1 enables cancer cells to tolerate accelerated cell proliferation. In the long term, we hope our research will lead to the development of new clinical trials in lung cancer that combine PRMT1 inhibitors with other agents.
Researchers will further investigate this connection between PRMT1 and the replication stress response. They will then be able to identify patients most likely to benefit from these drugs and design smarter combination therapies.
Professor of Molecular Genetics
Staff profile for Professor Jo Morris, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham.
Professor of Cancer Cell Biology
Staff profile for Clare Davies, Professor of Cancer Cell Biology, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham
