Breast cancer drug may hold key to tackling most deadly type of melanoma

Breast cancer drug may hold key to tackling most deadly type of melanoma

23 July 2019

Barbara Holland tried everything to stop headaches for months before her doctor sent her for an MRI. Her scans showed a tumour in her sinus passages, and four tumours in her brain. In August 2015, she was diagnosed with mucosal melanoma.

Mucosal melanoma, which occurs on the inner surfaces of the body such as the mouth, nose and anogenital region and is not linked to UV exposure, has a very poor prognosis with less than 20% of patients surviving five years after diagnosis.

Now, an Australian-led international team of researchers has discovered that a drug traditionally used to treat a type of breast cancer may hold the key to treating this aggressive and deadly form of melanoma.

The international study, led by researchers from Melanoma Institute Australia, QIMR Berghofer Medical Research Institute and The University of Sydney as part of the Australian Melanoma Genome Project, has uncovered the diverse genetic drivers for mucosal melanoma as well as identified potential treatments.

Lead study author Professor Richard Scolyer, Co-Medical Director Melanoma Institute Australia, The University of Sydney and Royal Prince Alfred Hospital says the study allowed researchers to not only look for new drug targets, but to also match available targeted drugs to the specific genetic drivers in mucosal melanoma.

“We now understand the genetic drivers of mucosal melanoma, and can match those to potential treatments,” Professor Scolyer said. The study revealed that a currently available class of drug commonly used to treat breast cancer looks promising for treating mucosal melanoma.

“The ramifications of this study are immense and are critical in us reaching our goal of zero deaths from melanoma.”

Published online at Nature Communications, the study detailed the genetic analysis of 67 mucosal melanoma tumours from patients from Australia, China, the United States and Europe. Using both whole-genome sequencing and whole-exome sequencing, the authors identified diverse drivers that suggested that mucosal melanoma has potential therapeutic targets.

The majority of mucosal melanomas sequenced in the study showed potential susceptibility to currently available classes of drug. One in particular, CDK4/6 inhibitors, are a class of drug used to treat HR-positive, HER2-negative breast cancer.

“While advancements in treatment have drastically improved survival outcomes for cutaneous (or skin) melanoma patients, those treatments do not work as well for mucosal melanoma patients,” Professor Scolyer added.

“But now we can build our treatment arsenal for this group of patients – starting with CDK4/6 inhibitors used to treat a subtype of breast cancer.”

The study also found possible reasons why mucosal melanoma is less responsive to immunotherapy which has had such success in saving the lives of UV-related melanoma patients. It revealed that a mutation in some mucosal melanomas locks immune cells out of the tumour, rendering immunotherapy treatment ineffective.

“I’m one of the lucky ones,” said Barbara.

The tumour in her sinuses was removed with surgery, and after three years of immunotherapy, one of her brain tumours is no longer measurable and the others are stable.

“This news is so exciting for other mucosal patients and their families. Hopefully in the near future, they will be able to have the same positivity that I have.”

While rare in Western populations like in Australia, where it makes up less than 2% of all melanoma cases, mucosal melanoma makes up a third of all melanoma cases worldwide.

A previous study also coming from the Australian Melanoma Genome Project found that mucosal melanoma is not linked to UV radiation, as is the case with cutaneous (or skin) melanoma.

There are no known risk factors for mucosal melanoma, making prevention strategies difficult. It is also usually diagnosed at a later stage of disease due to the challenges of monitoring sites where it is found – the internal surfaces of the body.

“The next exciting step is for Melanoma Institute Australia to develop a clinical trial to test classes of drugs and their effectiveness for treating mucosal melanoma,” said study author Professor Georgina Long, Co-Medical Director Melanoma Institute Australia The University of Sydney and Royal North Shore Hospital

“This is the new frontier in melanoma treatment, with very real benefits for patients internationally, and we are proud to be leading the world in saving lives.”

Barbara is no longer on treatment and comes to MIA for three monthly scans.

“It’s amazing to know that there could soon be new treatments for this horrible disease. I think the best part about this discovery is that it gives hope,” said Barbara.

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