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Cell by Cell

Personalised medicine is giving hope to people with melanoma.

Cell by Cell

Twice a year, I strip down to my underwear, don a paper gown and subject myself to a full-body examination at the dermatologist’s office. These are done twice as often as most other patients – and for good reason. Not only am I freckly and fair-skinned, I’ve had an unhealthy relationship with the sun, which makes me more susceptible to skin cancer.

During my teens and 20s, when I was a lifeguard, I spent the majority of my summers outdoors. Like my peers, I’d wanted to achieve the perfect tan. I’d worn sunscreen, but it was SPF 4 – barely any protection compared with what doctors recommend today.

Now I’m paying the price. This past decade, I’ve had a handful of suspicious-looking moles removed. Recently, my dermatologist sent me to a medical photographer for a full-body photo session to document my moles, in case they change.

My situation isn’t unique. Countless people worldwide didn’t protect themselves adequately from the sun’s ultraviolet rays during their youth. Decades ago, doctors didn’t preach about sun protection, and researchers didn’t realise that the sun’s ultraviolet rays could cause skin changes that can lead to melanoma, the deadliest form of skin cancer.

“The most important reason for the increase in melanomas is thought to be due to increased exposure to ultraviolet radiation from sun and artificial tanning sources,” says Dr John J. DiGiovanna from the dermatology branch of the US National Cancer Institute’s Center for Cancer Research in Maryland.

 

Sun exposure
Australia and New Zealand have the highest rates of melanoma in the world – melanoma being the third most commonly diagnosed cancer in Australia, and the fourth highest in New Zealand.

According to Cancer Australia, in 2016, over 13,000 new cases of melanoma will be diagnosed in Australia. In New Zealand, over 4000 new cases are confirmed each year.

A University of Queensland study published this year compared the rates of invasive melanoma in six populations – including Australia and New Zealand – over a 30-year period from 1982 to 2011. It found that while New Zealand’s rate of melanoma had increased to 50 cases in 100,000 people, Australian melanoma rates had fallen overall to 48 cases in 100,000 people.

“The main reason for this decline is that Australia has put a huge effort into prevention campaigns since the 1980s,” says Professor David Whiteman, who led the study. “Australians have become more aware of the dangers of melanoma. This has contributed to a decline in melanoma rates in people under 50. Unfortunately, rates of melanoma are still increasing in people over 50 [who] already sustained sun damage before the prevention campaigns were introduced, and those melanomas are only appearing now, decades after the cancer-causing exposure to sunlight occurred.”

But even if you’ve endured decades’ worth of sun exposure, there is hope.

 

Early treatment
The earlier you notice melanoma, the greater your chances are of being cured. Surgery is the primary treatment for early-stage melanoma.

“If you picked up an early-changing mole, you could have a virtually normal life expectancy,” says Girish Patel, lead investigator for the Skin Cancer Stem Cell Research Programme at Cardiff University.

Regular skin checks and lifestyle changes to limit further damage from the sun help improve the odds.

Since Imogen Cheese, 37, was diagnosed with stage II melanoma in 2013, she’s screened by her medical team every three months. “I cover up to avoid the midday sun,” says Imogen. She also wears sunscreen with a high SPF, is active and eats a healthy diet. So far, her cancer has not progressed.

 

Targeted therapy
Researchers have made great strides in the treatment of advanced melanoma. One option: targeted therapy, which can be given to stage IV patients with specific genetic mutations.

Australian melanoma researchers have been involved with targeted therapy studies since the beginning, about seven years ago.

“We do testing on their tumours to look if there are any mutations in certain genes in the tumour,” says Dr Alex Menzies, a medical oncologist at Melanoma Institute Australia.

“We have targeted therapy that can attack the BRAF mutation [which accelerates tumour growth], found in about 50 per cent of tumours …. If we give tablets for BRAF-mutant melanoma, almost every patient will have shrinkage of the tumour. On average, it will keep things under control for one year, and the one-year survival rate has improved to 70 per cent, from 30 per cent five years ago.”

Five years after John Ambrose, 67, had a stage-IV skin melanoma removed he began coughing up blood. His disease had spread to both lungs and his prognosis was poor. He joined a targeted therapy clinical trial in 2013, and within three months, his tumours shrank by 70 per cent. After 18 months, he had clear scans. Today, John travels, plays golf and spends time with his grandchildren. “My situation has not stopped me living a normal life,” he says.

Jesse Thomas, 57, also benefited from targeted therapy after being diagnosed with stage-IV melanoma in 2013, with tumours on his neck, liver and spine. Genomic testing revealed Jesse had an uncommon V600K BRAF mutation, and his oncologist was able to pinpoint a targeted therapy for him.

“They expected the cancer to stop growing, but it actually shrank,” Jesse says. “There’s no way to cure it, but I am controllable.”

Targeted therapy is only for stage-IV patients, but researchers are studying its effects on stage III patients.

 

Immunotherapy
Researchers have been able to stimulate the T-cells in some melanoma patients’ immune systems to fight cancer, with astounding results.

“T-cells kill off viruses,” Menzies says, “but with cancer, they’re sitting there around the tumour, asleep. They know that the tumour is ‘foreign’, but the tumour has turned them off, stopping them from killing it. Immunology drugs turn on the T-cells and they kill the tumour.”

Melanoma researchers consider immunology the biggest breakthrough in decades.

“This is our ‘penicillin moment’ in oncology,” Menzies says. “Melanoma can be turned into a chronic disease. Many people will not die from it if we continue to go the way we’re going.”

Immunotherapy doesn’t work for everyone, but it can be quite effective. Cardiff University’s Patel says, “In the 45 or so per cent of people who respond, they can respond for very long periods of time.”

In 2013, Vicky Brown, 62, was shocked to learn that a lump in her breast was actually melanoma, not breast cancer. She’d had early-stage melanoma in 2006, which returned in her breast and lungs.

Through a clinical trial, Brown received intravenous doses of two immunotherapy drugs. Her tumours shrank within weeks. Brown discontinued the drugs due to side effects, but it kept the melanoma in check for a year. In 2015, after new lung tumours appeared, she received more immunology treatments. The drugs again shrank her tumours.

“I am hoping this couple of doses will give me more time again,” Vicky says.

Researchers are working to get more patients to have a positive response to the treatment. “The notion is that clearly, if we can do it in a few, we should be able to do it in the majority,” says Patel.


Personalised medicine
For years, researchers tried creating a melanoma vaccine, to no avail. Now, researchers are combining the success of immunotherapy with the concept of vaccines, leading to personalised melanoma treatments.

“As we better understand how the immune system recognises melanoma cells, we are developing so-called personalised vaccines,” says Dr John Haanen, head of medical oncology at the Netherlands Cancer Institute in Amsterdam. “We are starting now in metastatic patients and if this concept works we’ll move to earlier stages.”

Hein Jambroers, 50, has benefited from a personalised treatment called adoptive cell therapy (ACT). He was diagnosed with stage-II melanoma in 2009, but a year later, he had stage-IV disease, with tumours on his right leg and liver, and was told that he had less than six months to live.

After getting some short-term benefit from targeted therapy, Hein was referred to an ACT clinical trial in 2011. Doctors harvested some of his white blood cells, then monitored them in a laboratory to identify the healthiest T-cells to fight melanoma. They were replicated in large numbers. Hein received chemotherapy to kill his existing T-cells, then got an infusion of the laboratory-created T-cells, which basically gave him a new immune system that shrank his tumours within three months.

He’s what doctors call a ‘complete responder.’ He’s had clean scans ever since; no trace of melanoma.

“Complete responders have an excellent prognosis,” says Haanen, who treated Hein. “‘Cure’ is always difficult to say, but very long-term remissions – which could be a cure – are seen in the majority of complete responders and in some partial responders.”

Hein, who expected to die, is cautiously optimistic. “I’m very positive about my future, but I’m always on a state of alert,” he says.

 

Stem cells
Soon, doctors may defeat cancer by attacking stem cells.

Skin stem cells make thousands of healthy skin cells. Melanoma stem cells work similarly, except they make thousands of malignant melanoma cells. Researchers are targeting melanoma stem cells to stop tumours from spreading.

“It’s like killing off the queen bee,” Patel says. “The whole hive then dies away, because you’ve gotten to the cell that’s giving rise to everything.”

This is vastly different from chemotherapy, which aims to kill as much cancer as possible. Stem cells make up only one to three per cent of some skin cancers.

“If you got rid of the cancer stem cell population, the whole tumour could not proliferate,” Patel says. “If you take the bulk of a tumour and regrow it in a mouse without stem cells, it can’t form. But if you take a small part of the cancer stem cell population, it grows back fully.”

Researchers have begun clinical trials, and treatments could be available in a decade.

Despite the sun damage that I endured during my youth, I’m optimistic that I’m doing everything that I can to stay ahead of any problems that may crop up. I’ve got photos of all of my moles and freckles now, which I use for monthly self-exams. I’ll bring them to my dermatologist for my next full-body examination. I’ve also been raising my children with 21st-century values for sun exposure – plenty of high-SPF sunscreen, hats and time in the shade – so hopefully the next generation won’t have the melanoma worries that my generation does.

After a Diagnosis
If you’ve been diagnosed with advanced melanoma, here’s what patient advocates recommend:

  • See a specialist
    Seek out a facility where doctors specialise in melanoma. “Our recommendation for patients is to get into a melanoma centre of excellence,” says Bettina Ryll, founder of Melanoma Patient Network Europe. “The new immunotherapies have very different side effects from anything we’ve ever had before, so you don’t want to have a physician who has never seen this.”
  • Consider a clinical trial
    Availability of immunotherapy and targeted therapy varies. Many patients enter clinical trials to receive these drugs. A promising clinical trial may be further from home than you’d prefer, but the extra drive could be worth it. Rory Bernard, 47, travels four hours for targeted therapy treatments, which have shrunk his tumours and extended his life.

Guarding Against Melanoma

  • Shun the sun Cover up and stay in the shade between 11am and 3pm, especially during summer, to limit damage.
  • Wear sunscreen Apply a broad-spectrum sunscreen (at least SPF 30) to exposed skin before going outdoors; reapply regularly, particularly after swimming.
  • Know your body Keep an eye on your moles, and see a dermatologist if any spots change.
  • Get skin exams Have a full-skin exam by a dermatologist or a GP with specific training in skin cancer at least once a year if you have special risk factors; every six months for anyone who’s had a skin cancer.
  • Avoid tanning beds They’re associated with melanoma.


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