Beating lung cancer—one gene at a time

The reality of his experience over the last ten years or so has surpassed his expectations.

“It has been an incredible time to be involved in this area. The progress over the last decade in lung cancer has been even more than I ever could have imagined,” he says.

Lung cancer is a complex disease consisting of many forms of cancer, where different treatment approaches are needed for the best chance of success. Many of the advances achieved to date are thanks to the range of new and innovative treatment approaches — including immunotherapies and gene-targeted therapies — that have come to the forefront in recent years.

“Here’s what’s changed: We are seeing that when we understand the biology of the cancer at a very fundamental level, then we can design therapies that are very specifically targeted to that biology,” says Dr Doebele. “While not all lung cancers are linked to specific genes, this approach has been transformative and is already making a huge difference, including for many patients with very advanced or difficult-to-treat cancers.”

One of Dr Doebele’s patients is Claudia Pearson, who works for a wilderness school in Lander, Wyoming, and is a keen mountain biker, horse rider and hiker. She first became concerned when she noticed some unusual symptoms.

“I remember I had vision issues in my left eye and, at times, no peripheral vision at all. I was weak and wobbly with my balance,” says Claudia. It was the concern of her co-workers that finally prompted her to get herself checked out in late November 2016. “It was then that I discovered that I had a lesion in the lower right lobe of my lungs and others in my brain. It was a real shock but I remained stoic, possibly because I was in denial,” said Pearson.

After the lung cancer diagnosis, Claudia had some initial treatment with radiotherapy, but without great success. She was then referred to Dr Doebele, who suggested genetic testing to find out the root, biological cause of her cancer. This was a transformative moment for Claudia as the results revealed that her cancer was driven by a rare mutation, or fusion, in her ROS1 gene.

“ROS1 is a gene that most of us have, but actually has a completely unknown function,” explains Dr Doebele. “When it is mutated — that is, when it undergoes a change in its coding — it becomes permanently activated or ‘switched on’. That causes cells to grow abnormally and to spread, which can lead to cancer.”

Claudia is in a rare minority — only 1 to 2% of non-small cell lung cancer patients have the activated ROS1 gene fusion — but for those who do, there are now reasons to be hopeful. The revelation from her genetic test meant that Claudia was able to join a clinical trial, testing a new treatment designed to target that exact genetic mutation.

“This trial was a godsend for my continued longevity,” she says. “Dr Doebele has been so kind, supportive and knowledgeable. I am feeling very hopeful about the future.”

Dr Doebele believes that stories like Claudia’s are becoming more and more common, as progress in precision medicine translates into the most precious outcome possible — more time.

“When I started in this field a decade ago, many patients lived for only 10-12 months,” he says. “Now we see many of our patients surviving for five years and beyond, which is amazing. And we know with targeted medicines that we don’t have to treat 100 patients to see one of them benefit — we can pick that one patient out before we start.”

The next big challenge is to ensure that every lung cancer patient is tested for specific genetic markers such as ROS1. “The great thing is that we are moving towards next-generation sequencing assays, where we can diagnose many genes at once — so not just ROS1 but a whole range of genes that could help to determine the treatment required,” said Dr Doebele.

Dr Doebele believes that we are only at the beginning of the journey with personalised cancer medicines and that one day, treatment could be unique from person-to-person.

That could mean more patients, like Claudia, responding well to treatment, and feeling hopeful about the future.