Past projects

LATe TreatmENT related Toxicity in Melanoma (LATENT)

Clinical Investigators

Dr Kate Young, Consultant Medical Oncologist, Royal Marsden Hospital, London
Dr Aislinn Macklin-Doherty, Post-doctoral clinical research fellow, Royal Marsden Hospital, London
Dr Sowmya Cheruvu, Clinical Research Fellow, The Royal Marsden Hospital, London
Dr Javier Pozas, Medical Oncologist, Clinical & Research Fellow, The Royal Marsden Hospital, London

Co-Investigators

Professor James Larkin, Consultant Medical Oncologist, Royal Marsden Hospital, London
Dr Anna Olsson-Brown, Consultant Medical Oncologist, The Clatterbridge Cancer Centre, Liverpool
Dr Rebecca Lee, Senior clinical lecturer medical oncology and Wellcome early career fellow, University of Manchester/The Francis Crick/University College London

Project start date

01/09/2023

Proposed project duration

1 year

Project Summary

Enormous advances in melanoma treatments have been made in the last decade, with the introduction of new immunotherapy and targeted treatments. This has revolutionised survival and there are now a growing number of people treated for advanced melanoma living many years after their diagnoses. However, there is a lack of knowledge about how these treatments affect people in the long-term, once their cancer is controlled.

This study will use different methods to collect and analyse data and address this gap in knowledge. The overall objective would be to publish results of these late-effect frequencies and risk factors discovered in this study in order to work towards setting up a larger multi-centre study investigating both medically reported and patient-reported late effects.

The main aims of the research project:

Setting up a large, pooled database of Royal Marsden, Clatterbridge and Christie long-term survivors treated for melanoma, detailing the type and frequency of late effects of melanoma treatments.

Investigating the use of immunosuppressive treatments and the pattern of referrals to specialists.

Investigating risk factors for a range of side effects in order to develop follow up guidance for late effects management for healthcare professionals.

Undertaking a literature review and public engagement events with patients, researchers and healthcare professionals to determine an optimal Patient-Reported Outcome Measures (PROM) collection tool.

The funding from Melanoma Focus is to be able to:

Support a clinical research fellow to carry out the data collection and analysis to fulfil the different aims of the project.

There is a commitment to collaborate on late-effects of immunotherapy research with the Melanoma Focus funded project Immuno-tox (see above).

Comment from Clinical Investigators

“This generous grant from Melanoma Focus will enable our research fellow to collect data from 3 leading cancer centres and information from patients themselves to improve our understanding of the long-term side effects and impact of immunotherapy treatment, to help us design and plan better follow up and survivorship services for our patients in the future.”

Project Update, December 2025

The full LATENT paper was published in July 2025.  

Late-Onset Immune-Related Adverse Events in Patients with Advanced Melanoma: The LATENT Study (https://doi.org/10.3390/cancers17152461) 

The experience with LATENT and knowledge gained is now feeding into the e-Immune project, being led by Prof Janet Brown in Sheffield (E-IMMUNE Programme – Meet the Team).  

The team at the Royal Marsden are also building on the experience with new studies looking at late cardiac toxicity (CARD-IO, open) and the impact of CPI on fertility and neurocognition (in development). 

The LATENT clinical fellow also worked simultaneously on a study on PROMs (Patient Reported Outcome Measures), led by Susanne Cruickshank’s team at the Royal Marsden Hospital, which has also been published: 

Identification of the PROMs used to assess ICI toxicities and HRQoL in patients receiving immune checkpoint inhibitor treatment in cancer care and their suitability: A systematic review (https://doi.org/10.1016/j.ctrv.2024.102862) 

Other related articles: 

1852P The use of patient-reported outcome measures to assess toxicities and quality of life associated with immune checkpoint inhibitor therapy: A systematic review – Annals of Oncology (https://doi.org/10.1016/j.annonc.2024.08.1947) 

1846P Social determinants of health in studies assessing toxicities associated with immune checkpoint inhibitor treatment: A systematic review – Annals of Oncology (https://doi.org/10.1016/j.annonc.2024.08.1941) 

A qualitative exploration of the lived experiences of patients who have received immunotherapy for metastatic melanoma and the support they received.

Clinical Investigators:

Delia Sworm, Trainee Advanced Clinical Practitioner Oncology Skin Cancers; St Luke’s Cancer Centre, Royal Surrey County Hospital
Postgraduate Student, MSc in Advanced Clinical Practice, University of Surrey,

Project start date

04/2022

Proposed project duration

6 months

Project Summary

Historically metastatic melanoma has been ‘chemotherapy resistant’ with a poor overall survival rate. Over the last decade, there has been a significant improvement in survival due to the introduction of single-agent and dual combination immunotherapy.
This research project aims to explore the lived experiences of patients during and after completing a course of immunotherapy for metastatic melanoma.

The main aims and objectives of the study

• To explore and understand the lived experiences of patients during treatment for metastatic melanoma.
• To identify the key issues and challenges they face once they have completed treatment, and what matters most to them (both during and post treatment).
• To describe the support patients received during and post-treatment and explore their perceptions of that support.
• To explore if there were any questions or concerns that they had about their experiences of immunotherapy and the care that they received, but they felt unable to ask (e.g., because they lacked confidence, knowledge, felt too anxious to ask).

The study will interview up to 10 participants recruited via an independent patient support group which covers the Surrey and Sussex Cancer Alliance geographical area. The interviews will be conducted online or by telephone using a semi-structured topic guide. Participants will be purposively recruited at varying time points post-treatment with an approximate time frame of three, six and 12 months plus.

The study will offer the participants an opportunity to convey their experiences and thus contribute to the evidence base. It is anticipated that the study will enhance the understanding of patients’ needs both during and post immunotherapy for metastatic melanoma and positively influence future practice.

The funding from Melanoma Focus will allow:

This Melanoma Focus funded research project will be submitted to the University of Surrey as the Lead Researcher’s MSc dissertation. Furthermore, the research results will be submitted to a peer-reviewed journal for publication, presented at conferences, seminars, and professional forums.
It is anticipated that research findings will allow for deeper insights into the human experience of the participants’ cancer journey by exploring their inner experiences. This, in turn, will translate to clinical practice and help to identify training needs and initiatives required to improve local and national service delivery.
The study will also generate ideas for future research in this rapidly evolving area.

Comment from Clinical Investigators

‘’I am hugely grateful to Melanoma Focus for the funding of this project which will enable greater insight into patients’ perspectives and experiences’

 

Project Update, October 2025

Using an interpretative phenomenological qualitative approach, ten individuals who had received immunotherapy for metastatic melanoma were interviewed. Interviews were transcribed and analysed for themes utilising an inductive approach. NVIVO software facilitated further analysis and categorisation of data.

Results:

The experience of living with a diagnosis of metastatic melanoma and receiving immunotherapy negatively impacted participants across the following themes: maintaining a normal life, psychological and cognitive, physical and social support. The study highlighted unmet needs in terms of information and support of these patients.

Conclusion:

Individuals living with and beyond a diagnosis of metastatic melanoma would benefit from access to support in terms of information and education, particularly when presenting with symptoms of treatment toxicities and during the transition phase post-immunotherapy. Further longitudinal research is needed to provide real-time insight into patient experiences throughout the treatment trajectory and survivorship beyond immunotherapy.

Identifying the costs and consequences of the diagnosis and management of melanoma – to assess the impact of melanoma prevention programmes

Clinical Investigators:

Katherine Payne, Professor of Health Economics

Co-Investigators

Martin Eden, Research Fellow in Health Economics
Louisa Gordon, Associate Professor in Health Economics
Adele Green, Professor of Epidemiology
Paul Lorigan, Professor of Medical Oncology

Project start date

12/2021

Proposed project duration

6 months

Project Summary

Preventing melanoma from occurring is far better than having to treat it. Evidence-based public health campaigns are aimed at reducing melanomas by removing exposure to ultraviolet radiation including from indoor tanning (sunbed) facilities. Sunbed use for cosmetic purposes causes melanoma affecting quality and length of life and imposing significant financial burden on healthcare systems. However, policies to ban commercial sunbeds and reduce melanoma must be shown to have a positive impact on NHS costs and patient health before being considered by governments.

This study, that is tailored specifically to the UK, feeds into a global agenda to prevent melanoma caused by the use of commercial sunbeds. It builds on the published work of co-investigators Gordon and Green, including studies that led to commercial sunbeds being banned in Australia.
This research is a vital step on the move towards implementing legislation to ban removal of sunbeds for public use in the UK, which is hoped will achieve wide benefit by reducing the number of patients diagnosed and living with melanoma in the future.

The main aims of the study

This project aims to gather information for the effectiveness and costs of diagnosing, treating, and monitoring different stages of melanoma based on current UK clinical practice.These data will then be used to update a published analysis assessing the impact of reducing the use of sunbeds on the costs and health-consequences of the management of melanoma.Preventing melanoma development through public health initiatives will save many lives, reduce the related morbidity and avoid unnecessary NHS spending. Ultimately, this proposed study will help promote the timely approval of health-improving interventions for use in UK healthcare system.

The funding from Melanoma Focus will allow:

The initial cost-effectiveness analysis to be updated with costs of current melanoma diagnosis and management practices.

Comment from Clinical Investigators

“The support from Melanoma Focus is crucial to enable us to generate the data needed to understand the impact of removing access to commercial sunbeds supported by a public health campaign. This work will be a step towards the goal of reducing the number of melanomas and the harmful consequences on people and healthcare systems.”

Project update, June 2023

The data collection and analysis for this project are now completed.  

The project has mapped diagnosis and treatment pathways for the dermatological, surgical and oncological management of melanoma. This is to help the researchers understand how many people within the population would follow each route through the treatment pathways.  

The proportion of people receiving each intervention in the relevant pathway was estimated, and then online interviews were used to conduct the exercise and collect the data from each expert. Seven dermatologists, five oncologists and four surgeons completed the exercise (August 2022-February 2023). 

For each proportion of people in a population receiving each intervention in the relevant pathway, a group estimate was generated so that it could be multiplied by intervention costs (price year 2021-22) to estimate the mean cost of treating a patient by management phase (dermatological, surgical and oncological).  

The next step is to use these results and update a published model which can show the cost-effectiveness of a policy-based invention to reduce melanoma and other skin cancers associated with indoor tanning.

Validation of Ambra-1 and Loricrin as prognostic biomarkers for the early detection of high-risk melanomas

Principal Investigators:

Dr Rob Ellis, The James Cook University Hospital, Middlesbrough and Institute of Cellular Medicine, Newcastle University
Professor Penny Lovat, Institute of Cellular Medicine, Newcastle University

Co-Investigators

Dr Marie Labus, Business Development Manager, Research and Enterprise Services, Newcastle University

Summary

 If melanoma spreads (or ‘metastasises’) from the skin to other parts of the body, the prognosis or likelihood of recovery will be affected. Thankfully, most patients can be cured if their melanomas are surgically removed from the skin before this happens. Analysing melanomas after their removal can help clinicians predict which patients remain likely to develop metastatic disease. Currently the accuracy of using this method for prognosis is not exact.

Loss of the surface layer of the skin over a melanoma is known as ulceration. Patients whose melanomas become ulcerated have a worse outcome, but the exact reason for this is unclear. In an initial group of melanoma patients, it was shown that the loss of two proteins, Ambra-1 and loricrin, in this skin layer is linked to the development of ulceration, and a greater risk of the disease spreading.

This research project looked for changes in these two proteins in the ulcerated skin layer of melanomas from a large group of patients. The aim was to find out how to predict which patients are at a higher risk of metastatic melanoma, and who will therefore need to be followed up more closely by clinicians after surgery.

The researchers gained a better understanding of the link between these proteins and skin ulceration, as well as their relationship with another protein, known as transforming growth factor beta-2 (TGFβ2). TGFβ2 is linked to how cells in the body grow and divide and is found in melanomas. Gaining understanding of these proteins may help to develop new treatments for patients who are identified as being at higher risk of disease spread.
Discovering earlier and more effective therapies would reduce the rate of metastasis and overall mortality from this most serious form of skin cancer.

Comment from Principal Investigators

“We are extremely delighted to receive this award as we feel that the results we have seen in a previous cohort of patients, as well as multiple laboratory experiments, suggests that we may have begun to unravel the enigma of melanoma ulceration. In doing so, we have identified two proteins in the epidermis overlying melanomas that when lost in the early stages of melanoma development suggest that a patient is at high risk of disease spread and higher mortality.
By further understanding this process, we may be able to develop new drug treatments to prevent the spread of disease and so impact greatly on the mortality from the condition.
The support of the Melanoma Focus has enabled us to take this project forward, allowing potential patient benefit as soon as possible”

Next Steps

The project resulted in the first melanoma test to identify those at low risk of cancer spreading.
By applying the test – called AMBLor® – to the standard biopsy of the primary melanoma on its removal, patients who are at low risk of the disease reoccurring or spreading can be identified. Melanoma Focus are delighted to fund the initial research that developed this test – which may change the follow-up pathways for patients with stage 1a-2b melanomas.

The effectiveness of the AMLo test is yet to be fully evaluated by the NHS, BAD and NICE.  However, if endorsed, this test may be offered to early-stage melanoma patients to potentially reduce the need for some follow-up which will be great news for patients.

Update December 2023

AMLo Biosciences Ltd published a large-cohort international validation study, confirming that the combined biomarkers, AMBRA1 and loricrin (AMBLor® histochemical test) can be used to reliably classify stage I and II melanomas at low risk of progression.

In practice, this information may support a reduction in the need for these patients to have further invasive diagnostic procedures, lengthy follow-up or unnecessary drug therapy, thereby easing pressure on health systems and offering patients a personalised approach to their melanoma management.

The results were published in the British Journal of Dermatology. 

Strategic biomarkers for aggressive melanoma

Principal Investigators:

Professor Charlotte Proby, Medical Research Institute, University of Dundee

Co-Investigators

Dr Tim Crook
Dr Colin Fleming
Dr Mathieu Boniol
Professor Catherine Harwood
Dr Rubeta Matin

Summary

Melanoma in its advanced stages tends to spread (metastasise) to distant organs including the liver, lungs and brain. When this happens, it can become incurable and reduces the life expectancy of the patient significantly.
There is increasing evidence that the early and adjuvant use of systemic anti-melanoma drugs allows more effective treatment and better clinical outcomes. Development of simple, non-invasive tests (particularly blood tests) to detect metastatic disease before the patient develops symptoms is therefore a high priority for melanoma research. Tests have been developed in which changes in the DNA profile can be detected in blood samples from patients with metastatic melanoma.
The tests that have been developed only require a blood sample to be taken at a routine clinical follow up and are extremely sensitive and specific for detection of metastatic melanoma.

This research project wants to increase how useful these tests are by including additional genes (identified in their laboratory) that may increase the effectiveness of the test and greatly increase the number of patients tested. This will mean the tests can be improved to a level that they will be useful for testing patients in melanoma clinics.
By achieving this it would mean that these blood tests can be introduced into routine clinical practice. This will increase the detection of metastasis that don’t show up on current standard tests and would help to initiate a change in the treatment of patients with metastatic melanoma, for example, being able to use drugs to treat the melanoma earlier rather than later.
The researchers believe that this would result in markedly improved clinical outcomes.

Comment from the Principal Investigator

“This Melanoma Focus funded research was very productive leading to 4 publications revealing epigenetic mechanisms involved in melanoma progression and metastasis (see below).
We made good progress in better understanding the epigenetic mechanisms that drive melanoma metastasis, but this work has not led to a commercially exploitable test for a variety of reasons, one being the introduction of adjuvant systemic therapy for high risk melanomas. In terms of defining melanoma ‘risk’ (i.e., risk of lymph node metastasis), it has been superseded by work on gene expression profiling (GEP) and we are currently validating a clinic-pathological-GEP algorithm that appears to robustly identify those low-risk melanomas with a less than 10% risk of a positive SLNB. Ultimately, we are hopeful that this test will identify those melanoma patients who will benefit from adjuvant systemic therapy without the need to perform SLNB, as SLNB is an imperfect and potentially morbid procedure.”

References and Publications relating to this project

• Wang H, Lee S, Nigro CL, Lattanzio L, Merlano M, Monteverde M, Matin R, Purdie K, Mladkova N, Bergamaschi D, Harwood C, Syed N, Szlosarek P, Briasoulis E, McHugh A, Thompson A, Evans A, Leigh I, Fleming C, Inman GJ, Hatzimichael E, Proby C, Crook T. NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. Br J Cancer. 2012;106(8):1446-52. doi: 10.1038/bjc.2012.95

• Lo Nigro C, Wang H, McHugh A, Lattanzio L, Matin R, Harwood C, Syed N, Hatzimichael E, Briasoulis E, Merlano M, Evans A, Thompson A, Leigh I, Fleming C, Inman GJ, Proby C, Crook T. Methylated tissue factor pathway inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma. J Invest Dermatol. 2013;133(5):1278-85. doi: 10.1038/jid.2012. 493.

• Atkinson A, Renziehausen A, Wang H, Lo Nigro C, Lattanzio L, Merlano M, Rao B, Weir L, Evans A, Matin R, Harwood C, Szlosarek P, Pickering JG, Fleming C, Sim VR, Li S, Vasta JT, Raines RT, Boniol M, Thompson A, Proby C, Crook T, Syed N. The collagen prolyl hydroxylases are bifunctional growth regulators in melanoma. J Invest Dermatol. 2018; 139(5):1118-1126. doi: 10.1016/j.jid.2018.10.038.

• Renziehausen A, Wang H, Rao B, Weir L, Nigro CL, Lattanzio L, Merlano M, Vega-Rioja A, Del Carmen Fernandez-Carranco M, Hajji N, Matin R, Harwood C, Li S, Sim VR, O’Neill K, Evans A, Thompson A, Szlosarek P, Fleming C, Stebbing J, Proby C, Tzakos AG, Syed N, Crook T. The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention. Oncogene 2019;38(13):2320-2336. doi: 10.1038/ s41388-018-0563-y