1. Uncovering the significance of hypoxia in cancer science
A discovery so significant that it warranted a Nobel prize: Sir Peter Ratcliffe is famed for his work on oxygen deprivation (hypoxia) and subsequent cellular responses.
Cancers have unique microenvironments, which they must overcome in order to grow rapidly and uncontrollably. By understanding these conditions and how they come about, clinicians and researchers can strive to develop new drugs to reverse or suppress these pathways.
During his time in Oxford’s Nuffield Department of Medicine, Sir Peter discovered that a specific hormone, known as EPO, was involved in the production of blood cells in response to low oxygen levels in the kidneys. The underlying mechanism behind this process was later applied to cancer, and explained how cancers could create new blood vessels to sustain their fast and uncontrolled growth. This discovery was so significant, he was awarded the Nobel Prize in Medicine in 2019. Ratcliffe’s work into EPO has paved the way for the development of new drugs to improve the efficacy of cancer treatments.
NOW: Continuing this important work into tumour microenvironments, the Oxford ARCADIAN project is now investigating how common antimalarial drug Atovaquone can help to reduce the hypoxic environment of tumours and improve the efficacy of treatments such as radiation.
2. The discovery of regulatory T-cells (Tregs) told us a lot about how cancers can progress
Regulatory T cells (Tregs) are a specialized subpopulation of immune cells that act to suppress the body’s immune response. Because of this, their importance in the cancer development process cannot be understated. If there is a dysregulation in Treg frequency or function, diseases such as cancer can be allowed to thrive and progress. The discovery of Tregs has explained - in part - why the immune system does not effectively defend against tumour cells, as well as identifying a new avenue for targeted cancer treatment. Since their discovery, a taxonomy of new Treg subtypes with varying functionalities have been found, further diversifying the potential for new therapeutic targets.
NOW: Developments into Immuno-oncology remains one of the four priority cancer themes at the University of Oxford, with researchers at the interface between cancer and immunological sciences striving to unravel the mysteries of the immune system. As part of this dedication, the University looks forward to welcoming the launch of the upcoming Oxford Centre for Immuno-oncology in 2022.
3. Shaping public policy around the risk of smoking, diet & cancer
There are many potential environmental factors linked to cancer, but smoking and diet are two factors that are known for certain to significantly increase your risk. However, it took a long time for society to understand this risk, and for smoking cessation and diet to be integrated into public health policy.
Sir Richard Peto dedicated his research in Oxford to unravelling the connections between smoking, diet and cancer risk. Through his meta-analyses we have found key pieces of information that have contributed significantly to shaping public policies, such as showing that UK cancer death rates are still one-third higher than they would be if people didn’t smoke. He was also the first to describe the future worldwide health effects of current smoking patterns, predicting one billion deaths from tobacco in the present century if current smoking patterns persist.
He and his colleagues are running studies of millions of people followed for many years in many countries to assess the changing effects of smoking, drinking, diabetes and obesity on death from cancer and many other conditions. As the world’s leading expert on death related to tobacco, Sir Richards’s work in cancer was so significant, he even had a paradox named after him.
NOW: His work has inspired many more in Oxford to investigate the causational links between lifestyle and cancer, through the ongoing work of the Cancer Epidemiology Unit, European Prospective Investigation into Cancer and Nutrition (EPIC) and with international datasets such as the China Kadoorie Biobank.
4. Developing simple cancer blood tests and rolling them out into the NHS
Diagnosing cancer can take time. From the moment a patient sees their GP they may undergo rigorous and invasive testing, which take time and resources. As we learn more about cancer, we are finding unique features that allow us to develop new, simple tests to accurately and quickly diagnose multiple cancers.
Liquid biopsies, such as blood or urine, can be used to find trace-materials indicative of cancer. This is leading to a revolution in early-cancer-detection blood tests being developed and trialled in Oxford. Some researchers are developing tests to identify genetic material of cancers, whilst others are looking for cancer metabolites, and all are showing very promising early results.
NOW: Oxford is currently involved in the SYMPLIFY study – validating the use of one such blood test within the NHS. Initial results from the nationwide study are expected to be released by 2023. If positive, the study will be expanded to involve around 1 million participants in 2024 and 2025 before potential roll-out into the NHS for general use.
5. The link between HRT and cancer risk, and informing its use
Hormone replacement therapy (HRT) came as a blessing to many menopausal women in the late 1990s. However its discovery was somewhat dampened as results of the Women’s Health Initiative in 2002, which showed that HRT had potentially more detrimental effects than beneficial ones. Its association with increased risk of cancer meant that public and medical opinion quickly changed: its usage was quickly unrecommended, leading to negative consequences for the health and quality of life of menopausal women.
The work of Dame Valerie Beral and the Million Women Study (MWS) was quick to delve further into these cancer-related links, in order to better understand HRT and inform its usage. The MWS, opening in 1997, recruited more than 1.3 million UK women over 50, becoming the biggest dataset of its kind at the time.
Results from the study in 2003 confirmed the associated risk of HRT with certain cancers, such as breast cancer. But more importantly, the study also showed that risk increases the longer a woman uses HRT, but drops to the normal level within five years after stopping use. This discovery was significant in defining recommended length usage of HRT, and allowed patients and clinicians to weigh up the associated risks of HRT against the benefit to a woman’s wellbeing.
NOW: Dame Valerie’s legacy into improving women’s health continues in Oxford with the work of ovarian cancer researcher Ahmed Ahmed and the continuation of the Cancer Epidemiology Unit where her work originally took place.
6. Developing new drugs to treat historically difficult-to-treat cancers
Cancer treatments are never a one-size-fits-all solution. There is always a need to discover new therapeutic drugs that target specific cancer subtypes, or can treat cancers that do not currently have any effective treatment options. Researchers at the University of Oxford from departments such as Chemistry, Biochemistry, Pharmacology and Oncology are continuing to develop new treatments for patients with little or no viable treatment options.
NOW: The immunotherapy drug Tebentafusp has been tested in Oxford clinical trials and shown to improve the longevity of patients with metastatic uveal melanoma – a cancer that is historically hard to treat. Now in its Phase 3 of clinical trials it has become the first new therapy to improve the overall survival of uveal melanoma patient in 40 years, and will be applied to more cancers in the future as research progresses.
7. Discovery of the first tumour-specific antigens that went onto produce the first generation of anti-cancer vaccine
Finding molecules that are unique to cancers is an ideal way to create targeted treatments that don’t damage healthy, normal tissue. Discovering these molecules on multiple different tumour types is even more exciting as it can lead to the development of multi-cancer treatments.
NOW: The work undertaken by Benoit Van den Eynde at the Ludwig Institute in Oxford discovered tumour-specific antigens known as MAGE-A3 and NY-ESO-1, which were found on multiple different cancer types but crucially not on normal cells. This allowed the development of novel immunotherapy vaccines in collaboration with Adrian Hill, who co-developed the ChAdOx1 viral vector (famed for its use in the AZ-Oxford COVID vaccine). This collaboration has since seen the development of the first-of-its-kind cancer vaccine, which entered clinical trials in 2022.
8. Revolutionising the way we deliver drugs to a tumour
Traditional chemotherapy is released across the body, with only a fraction of the therapeutic reaching a tumour. As a result, it is associated with toxic side-effects that often lower a patient’s quality of life throughout treatment. Oxford researchers are finding novel ways to deliver lifesaving anti-cancer drugs in more targeted, direct ways. In doing so, clinicians can raise drug dosage and increase the chance of treatment success, without damaging healthy tissue and causing unacceptable toxicity to patients.
NOW: Ongoing projects such as PanDox and BUBBL are trialling novel ways to encapsulate anti-cancer drugs, and release drugs directly in and around tumours. These particular projects, lead by the Department of Engineering, are combining ultrasound, oncology and bubble technology to achieve this.
9. Implementing cancer risk scores into primary care
Not everyone will get cancer in their lifetime, but some people are at an increased risk due to genetic, environmental or other biological factors. Identifying these people by giving them a risk score would allow clinicians to prioritise patients for more regular screening, to increase the chance of early detection.
NOW: Oxford researcher Julia Hippisley-Cox has established risk scores for multiple diseases, including cancer, through her QResearch database. Utilising the plethora of information in patient medical records, Julia’s work has allowed for the identification of new cancer-related symptoms and develop risk-scores to prioritise patients using the tool QCancer. This tool was similarly used to prioritise patients for vaccination during the COVID pandemic, and is now used widely across the NHS to ensure people at risk are identified and monitored.
10. Pioneering the use of mammographic imaging in breast cancer screening
Human error is always a risk when diagnosing cancers. So there is a need to find new ways to analyse patients and the results of their medical tests (such as medical scans) that use reliable computer-based technologies. Whilst many Oxford researchers are exploring the applications of AI in analysis, Oxford’s contribution to this field began a lot earlier in the 1990s with Sir Mike Brady. Sir Mike switched from his field of robotics at MIT to the field of medical imaging after he saw, first hand, how important accurate medical image analysis is in early cancer detection.
Sir Mike continued his work in Oxford and became a pioneer into mammographic imaging of breast cancers. Sir Mike’s work focused on the mathematical modelling of X-rays and how they travelled through the female breast. This entirely novel ‘physics based’ approach became the basis for analysing digitised mammographic images and identifying cancer, which has since become part of standard UK screening.
NOW: Nowadays the University of Oxford has a wide variety of projects dedicated to medical imaging analysis. In 2020 the Government announced a £11 million, Oxford-based, AI research programme to improve the diagnosis of lung cancer and other thoracic diseases. The project, known as DART, will use AI to more accurately diagnose lung cancer from imaging data.
There are now over 1,000 Oxford researchers who dedicate their work to tackling cancer-related challenges, and continuing on the legacy of world-class cancer discoveries across our key themes.
As part of World Cancer Day 2022 we thank all the researchers, clinicians, administration and support staff who dedicate their time to finding new and improved ways to understand, detect and treat cancer.