by Sophie Mumford, research technician working with Prof Sarah Newbury at Brighton and Sussex Medical School (BSMS) 4th December 2017

Background

Recent funding from the Myfanwy Townsend Melanoma Research Fund has provided me with the exciting opportunity to work alongside Professor Sarah Newbury and her research team, to check and validate the microRNA biomarkers identified in these initial experiments.

The importance of early detection

Melanoma remains the most aggressive form of skin cancer with an increasing incidence worldwide. Survival rates depend heavily on the stage of disease at the time of diagnosis; when detected in the early non-metastatic stages (I and II), melanoma has good prognosis with a 5-year survival rate of 100% in stage I melanoma patients and 80%-90% in stage II melanoma patients, as thin local tumours are highly curable by surgical resection.

While surgical resection of a non-metastatic melanoma can result in disease-free intervals, recurrence is common often resulting in progression to locally advanced melanoma and subsequently to metastatic melanoma (stages III and IV), and a 5 year survival rate of ~50% in stage III melanoma patients and 10-25% in stage IV melanoma patients (Cancer Research UK).

This presents a pressing need to establish robust biomarkers that:

(1) Allow detection and diagnosis of melanoma in its earliest stages I and II, and

(2) Allow the identification of patients at high risk of metastatic recurrence after surgical resection of a non-metastatic melanoma.

Early detection will maximise the chances of patient survival, as there are now a number of treatment options available that are effective against certain subtypes of stages I, II and III melanoma.

The role of microRNA biomarkers

Circulating microRNAs are emerging as promising non-invasive cancer biomarkers. Previous work carried out at the Blond McIndoe Research Foundation and the Brighton and Sussex Medical School, identified 3 potential microRNA biomarkers that can distinguish Stage I/II from Stage III/IV melanoma, plus three potential reference controls.

 

Our progress

Since our previous report, I have analysed all of the data obtained from the 474 qRT-PCR assays quantifying the relative levels of the three potential biomarkers in RNA extracted from the serum of 20 healthy, 20 stage I/II and 20 stage III/IV donors. I re-extracted RNA from the same patient serum samples using a different miRNA extraction kit, and repeated the qRT-PCR assays to assess whether the RNA extraction method influences the detection of these specific microRNAs from our samples.

Additionally, I added the C. elegans miR-39 spike-in to control for any inconsistencies in the extraction efficiency between samples. I re-analysed the initial Exiqon microRNA Array data obtained at the beginning of this project and identified two additional potential biomarkers. I have analysed the levels of these two microRNAs between our three patient groups, again using qRT-PCR against the RNA extracted using both extraction kits.

Next steps

I am currently in the process of reviewing the literature on circulating microRNA biomarkers in melanoma, and the limitations of the circulating microRNA biomarker detection and analysis methods. I have designed a spreadsheet to document the microRNAs identified in these papers, as well as the detection and analysis methods used.

The information that I collect will be used to inform the introduction and/or the discussion in our publication. To assess the extraction efficiency of the two miRNA extraction kits used, I will collect serum from healthy donors, add the C.elegans miR-39 spike-in control and run an equal volume of each sample through each kit, followed by comparison using qRT-PCR.

Conclusion

Therefore we will obtain information on the consistency of the two RNA extraction used, which will be very useful for our further work and for other researchers in the field. The data for this experiment will be included in the publication we are currently preparing.

For further information on this report and the  relevant melanoma research work contained herein please contact Sarah Newbury at S.Newbury@bsms.ac.uk.

 

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Mr Siva Kumar

By Siva Kumar

I was delighted to be offered the opportunity to attend the World Melanoma Congress in Brisbane this year. This was a conference attended by over 1,000 medical practitioners and stakeholders, all of whom were involved and interested in the same subject, namely improving outcomes for people with melanoma.

The meeting, which was held in the Brisbane Convention & Exhibition Centre spanned four days and covered a breadth of topics ranging from prevention, cancer cell biology all the way through the pathway onto treatment and aftercare. This event was attended by the world’s leading experts on the melanoma. There was also a healthy representation from the United Kingdom, including Howard Peach from Leeds, Marc Moncrieff from Norwich and Alistair Mackenzie Ross from London.

Speakers

Key note speakers included Prof Georgina Long who gave an update and overview of the latest medical evidence for melanoma treatment in 2017. Dr Jerry Gershenwald talked through the new AJCC Melanoma Staging; a tool that is to be implemented by all units across the world from January 2018. Prof John Thompson from the Melanoma Institute of Australia talked about the evolving role of surgery, especially in Stage IV melanoma. And Dr Caroline Robert from the University Paris Sud discussed all the latest research in melanoma immunotherapy.

Immunotherapy

The headline topic was surely the emerging and evolving role of immunotherapy for the treatment of Stage III melanoma. Numerous trials that have been performed and are still ongoing which suggest that immunotherapy can be used successfully as the first line treatment for many patient with melanoma that has spread. In some instances it may replace the need for morbid surgery and this was a hotly debated topic at the sentinel node session.

The consensus was that Sentinel Node Biopsy has an even greater role to play going forwards in identifying patients at risk of disease progression as we now have the tools to potentially treat these patients at an earlier stage. The final results of the adjuvant immunotherapy studies are to be published in 2018 and all the data so far suggests there is improved survival when used in Stage III melanoma patients.

Prevention & detection

There was also a large focus on prevention and early detection.  It is well known that early detection of melanoma means less morbid surgery and a higher potential for cure.  Further to this, it is widely recommended that each person performs regular skin self-exams to look for new or suspicious spots, and seeing their GP immediately to evaluate anything changing, itching or bleeding on the skin.

Because unprotected exposure to UV light is the most preventable skin cancer risk factor,  the advice to everyone is to stay away from indoor tanning beds and seek protection from the sun’s harmful rays by using shade, wearing protective clothing and a broad-spectrum, water-resistant sunscreen; SPF30 or higher.

This advice is one of the founding aims of the Myfanwy Townsend Melanoma Research Fund; the charity that I represented at the event.

Getting social

The Australians have had a lot of success with their health campaigns. Their public health messages are directed by each state in Australia and it was clear that in Queensland, where melanoma rates are the highest, there has been a big emphasis on developing new and out of the box ideas to deliver sun protection messages.

Perhaps the thing that struck me the most was the role that social media will play in education, especially in the case of informing younger people, and the role that technology is being used in ever increasing ways to help screen skin lesions with much more accuracy than ever before.

Take for example a new Photoageing App for melanoma prevention developed by a dermatology team in Essen Germany. It is a fun tool to use and the author has taken this App to various schools as an educational tool to inform teenagers on the dangers of sun exposure and in particular sunbeds.

Artificial intelligence (AI)

Adrian Bowling from MoleMap gave an interesting lecture on artificial intelligence and its usage in screening the population for melanoma. He made a valid point stating that dermoscopy is time consuming and there are only a limited number of dermatologists. Each year MoleMap assesses 1 million lesions but finds just 250 melanomas.

Obviously, this is not an effective usage of human time and one solution would be to use computer assisted diagnosis with sophisticated algorithms that spot suspicious lesions that help direct dermatologists to perform a hands on clinical diagnosis.

The increasing use of confocal microscopy often in conjunction with dermoscopy is increasing the accuracy of detecting early and in situ melanoma. This has two effects; firstly, melanomas that are detected earlier using this technique receive treatment earlier with a better chance of cure. Also, it is possible to detect benign lesions more accurately, meaning fewer patients are undergoing unnecessary surgical excisional biopsy.

Dr Sebastien Debarbieux and his team in Lyon proved the worth of confocal dermoscopy in pigmented lesions of the nail matrix, an area that is difficult to clinically diagnose accurately without the need for a surgical biopsy.

Conclusion

In summary, I believe we can all learn, borrow and adapt many of these ideas to promote protection and prevention of melanoma here in the UK. This knowledge is something I will bring to the table in my work in the MASCU at Queen Victoria Hospital and in my role as medical ambassador for the Myfanwy Townsend Melanoma Research Fund.

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university of sussex melanoma skin cancer

Brighton and Sussex Medical School (BSMS)  working with the Myfanwy Townsend Melanoma Research Fund  – By Sophie Mumford

Melanoma remains the most aggressive form skin cancer with an increasing incidence worldwide. Surgical resection of a non-metastatic melanoma (stage I/II) can result in disease-free intervals; however recurrence is common often resulting in progression to metastatic melanoma (stage III/IV) and death within 5 years.

This presents a pressing need to establish biomarker signatures that allow identification of patients at high risk of recurrence, to enhance their likelihood of survival, as there are now a number of drugs available that are effective against certain subtypes of melanoma.

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Our medmr siva kumar 9th world congress of melanoma researchical ambassador Mr Siva Kumar is currently in Australia, representing both ourselves & Queen Victoria Hospital at the 9th World Congress of Melanoma.

This global summit was devised to accelerate scientific and clinical investigations into melanoma, providing an opportunity for people from all multi-disciplinary fields to meet and exchange knowledge and expertise.

Says Siva, “This is an outstanding event, providing real insight into unpublished work which is going to completely change the way we treat melanoma”.

We cannot wait to hear more from Siva on his return. To view the schedule of this 4 day event click HERE. 

Mr Siva Kumar on the forthcoming 9th World Congress of Melanoma

Although incidence of melanoma is still rising at alarming rates, when it comes to treatment we are living in encouraging times. There has been a big surge in the number of medical and scientific discoveries in recent years, focusing on the prevention, diagnosis, and management of this, the most dangerous form of skin cancer.

It is no exaggeration to say that melanoma treatment is also probably the fastest changing oncological field at present. This is why, as a melanoma surgeon I am honoured and excited to attend the 9th World Congress of Melanoma in Australia this October.

9th world congress of melanoma society for melanoma research

My trip – kindly sponsored by the Myfanwy Townsend Melanoma Research Fund – will provide me with the chance to learn and keep conversant with the latest research and trends. It will create unparalleled opportunities to network, offering endless possibilities of partnering with other leading clinicians and scientists from around the world, to exchange knowledge, fresh thinking, expertise and new ideas.

michelle baker ceo with siva kumar medical ambassador
Michelle Baker (CEO) with Siva Kumar (Medical Ambassador)

Having spent an enjoyable and successful year working with this highly proactive charity, raising awareness of melanoma in their ‘Watch your Back!’ campaign, I’m looking forward to sharing my experiences with my peers. It is proven that early detection of melanoma leads to better outcomes which is showcased by the fact that this impactful campaign is soon to launch in New Zealand.

When it comes to hot topics of discussion, the role of ‘sentinel node biopsy’ in the management of melanoma remains up there. As one of the leading members of the MASCU team at Queen Victoria Hospital in East Grinstead, that has recently introduced SNB to SE England, I will be keen to critically evaluate the recent evidence presented at the Conference, to ensure that patients treated at QVH can benefit and are fully informed.

I have no doubt there are other groups and charities around the world that will have innovative methods to spread a similar message.  I hope to come back with lots of ideas that I can share with the Myfanwy Townsend Melanoma Research Fund, and work with to implement in future campaigns.

For further details on the Conference and how this can impact the local community, please watch out for my updates at www.melanoma-fund.co.uk.

 

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university of sussex research sarah newbry Melanoma microRNA biomarker project

By Professor Sarah Newbury – Brighton and Sussex Medical School (BSMS)

Melanoma microRNA biomarker project
The overall aim of our study is to identify microRNA biomarkers from the circulating blood to detect recurrence in malignant melanoma. MicroRNAs (miRNAs) are small non-coding RNAs which are known to control cellular pathways through post-transcriptional control of gene expression.

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