Posts

Higher testosterone levels in men linked to greater melanoma risk

1 in 36 UK males and one in 47 UK females will be diagnosed with melanoma skin cancer in their lifetime. However, 86% of melanoma cases were preventable, as many cases are caused by UV ray exposure, but other factors can also play a role in who is most at risk, such as age and genetics.

A recent study lead by Dr Eleanor Watts at the Nuffield Department of Population Health has now found that testosterone is one of these risk factors. Published in the International Journal of Cancer, the team found that men with high levels of testosterone have an increased risk of developing a potentially deadly type of skin cancer. This was a result of studying blood samples hormone data. collected by the UK Biobank from 182,600 men and 122,100 postmenopausal women aged 40 to 69.

The researchers looked both the total level of testosterone in the blood samples, as well as levels that were freely circulating. They then used national registries and NHS records to explore whether participants went on to develop or die from cancer.

The results show that by 2015-16, after being followed for an average of seven years, 9,519 men and 5,632 postmenopausal women – 5.2% and 4.6% of participants respectively – had been diagnosed with a malignant cancer. By excluding other, non-melanoma diagnoses and accounting for other factors, they found that for men, higher levels of testosterone, whether freely or in total, were associated with a greater risk of developing malignant melanoma.

Specifically, each 50 pmol/L increase in free testosterone was found to raise the chance of developing this cancer by 35%. 90% of men included in the study had free testosterone concentrations of between 130 pmol/L and 310 pmol/L.

Among other findings, higher levels of freely circulating testosterone were associated with a greater risk of prostate cancer in men, while in post-menopausal women, higher levels of testosterone, whether freely circulating or in total, were associated with a greater chance of endometrial and breast cancer.

Dr Eleanor Watts, the first author of the research from the University of Oxford, says:

“There has been indirect evidence for testosterone and melanoma before, but this is the first time we have been able to look directly at the hormones in the blood

“Although we have seen associations of prostate, breast and endometrial cancer with testosterone before, this is the first time we have seen an association with risk of melanoma in men.”

 

About Eleanor

Eleanor is an Early Career Research Fellow in the Cancer Epidemiology Unit (CEU), part of the Nuffield Department of Population Health. Her research examines the role of endogenous hormones on prostate cancer risk using UK Biobank.

New melanoma drug a step closer to the clinic

Previous phase 1 and 2 clinical trials have been conducted into Tebentafusp, a new anti-tumour immune response drug for patients with metastatic melanoma. The results from Immunocore and the University of Oxford, found that this first-of-its-kind treatment showed great promise in helping the immune system fight off melanoma cancers of both the eye and skin. The phase 3 clinical trial for this drug is the first for an affinity optimised T-cell receptor drug, making it the first of its kind.

Today, Immunocore the company behind the drug have announced trial results showing tebentafusp works better for patients with untreated metastatic uveal melanoma, when compared to other treatment choices.

“A positive survival benefit for tebentafusp represents a major step towards bringing a potential new treatment for cancer patients with a high unmet need. If approved, it would be the first new therapy to improve the overall survival in 40 years and to be specifically used in the treatment of metastatic uveal melanoma, a disease with poor survival where new therapies are urgently needed”

– Bahija Jallal, CEO of Immunocore

Tebentafusp comes out of clinical trials led by Prof Mark Middleton (Department of Oncology). Now, we see the potential for this drug coming into the clinic, subject to regulatory approval, as early as next year.

“It is very exciting that our observations in the first trial of tebentafusp, that it could make some uveal melanomas shrink, have now been borne out in larger studies. There’s still a way to go but there is every hope that this will prove an option for the treatment of this difficult cancer quite soon.”

– Prof Mark Middleton, University of Oxford and the National Institute for Health Research Oxford Biomedical Research Centre.

Uveal melanoma is a rare and aggressive form of cancer that affects the eye, and typically has a poor prognosis and has no accepted optimal treatment and management. After the cancer metastases, 50% of patients have life expectancy of less than a year. Tebentafusp has the potential to be the first new therapy to improve the life expectancy of patients in over 40 years.

About the researchers

This research was funded by Immunocore.

Prof Mark Middleton is the Head of the Department of Oncology at the University of Oxford. He has overseen the development of internationally leading melanoma and upper GI clinical research groups and establishment of portfolios of early phase radiotherapy and haemato-oncology trials in Oxford. He is involved in the evaluation of novel immunotherapeutics, including pre-clinical development, trial design, proof of mechanism and proof of concept.

Immunocore, is a pioneering, clinical-stage T cell receptor biotechnology company working to develop and commercialise a new generation of transformative medicines to address unmet needs in cancer, infection and autoimmune diseases.  The Company’s most advanced programs are in oncology and it has a rich pipeline of programs in infectious and autoimmune diseases. Immunocore’s lead program, tebentafusp (IMCgp100), has entered pivotal clinical studies as a treatment for patients with metastatic uveal melanoma. Collaboration partners across the Immunocore pipeline include Genentech, GlaxoSmithKline, AstraZeneca, Eli Lilly and Company, and the Bill and Melinda Gates Foundation. Immunocore is headquartered at Milton Park, Oxfordshire, UK, with offices in Conshohocken, Pennsylvania and Rockville, Maryland in the US. For more information, please visit www.immunocore.com.

The National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) is based at the Oxford University Hospitals NHS Foundation Trust and run in partnership with the University of Oxford.

The NIHR is the nation’s largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. www.nihr.ac.uk/patientdata

 

Epigenetic markers for melanoma patient response to ICB therapy

Development fund winners Rosalin Cooper & Ben Fairfax are investigating the epigenetic landscape of melanoma patients and how it can impact patient sensitivity to ICB therapy

New melanoma cancer drug in development shows promise

University of Oxford and Immunocore Ltd have investigated Tebentafusp, a new anti-tumor immune response drug for patients with metastatic melanoma