health & science

Cancer treatment tailor-made for your tumour

Cancer treatment could be in for a paradigm shift with genomic profiling opening the door to personalised tumour therapy. Dr Nicholas Fleming explains how he plans to use fellowship funds to bring personalised treatment a step closer.

The days of a one-size-fits-all approach to treating tumours could be coming to an end.

Tumours are unique and two different people each with a tumour in the same part of their body may respond differently to the same treatment.

Sequencing a tumour's genome can aid in understanding its individual quirks and improve the chances of choosing an effective treatment.

University of Otago’s Dr Nicholas Fleming thinks spending $1000 to $2000 upfront to sequence a tumour could potentially save $100,000 worth of future treatment which might not even work for that particular tumour. 

Trouble is, in New Zealand this isn’t being done. 

“Overseas, many countries are sequencing all cancers which come through the door.”

When asked why not, Fleming struggles to come up with a compelling reason. 

“I think we’re just behind.”

He thinks tumours should be sequenced as part of a routine investigation into a patient’s cancer and believes with New Zealand’s relatively compact health system this approach could easily be adopted. 

Fleming has just been awarded $600,000 in funding via a Sir Charles Hercus Health Research Fellowship to help his work looking at three biomarkers which could predict what tumours will respond best to immunotherapy. 

Tumours and treatments

Traditionally, treatment for cancer can include surgery, chemotherapy, radiational therapy, hormone therapy or bone marrow transplants. 

A relative new kid on the block is immunotherapy, which uses drugs called immune checkpoint inhibitors. These first hit the market in 2011.

“They [immune checkpoint inhibitors] stop cancer cells from hiding from the immune system.”

Fleming describes checkpoints as a cloaking blanket that cancer uses to avoid detection by the immune system's police - T cells. 

“When the T cell comes along to kill them, the cancer cell says “No, I’m ok, I don’t need to be killed”.

Checkpoint inhibitors work by stripping the blanket away and unmasking the cancer. It’s then seen as something foreign by the T cells and promptly dispatched.

This type of treatment doesn’t work for all cancers and with drug patents lasting around 20 years, treating cancer with these new drugs is still costly. 

“One person's cancer may have 20 to 30 mutations, while the next person’s cancer may have 5000 mutations. The ones that have lots of mutations create more things for the immune system to see … it is those cancers that are responding to the immune checkpoint inhibitors.”

Is it easy to figure out how many mutations a cancer has?

“Yes and no," said Fleming.

"No, because that’s not done currently but the easy way is to do exactly what I’m suggesting and that is to sequence the whole cancer. If you spend that $1000 you can see how many mutations there are and you can predict whether that cancer is going to respond to immune checkpoint inhibitors.”

For others, chemotherapy might work better. Fleming describes this as a poison which kills any cells, such as cancer cells, that divide fast. 

“Now as we have a situation where we have these immune checkpoint inhibitors coming through and we’ve also got some patients that may actually do better on chemotherapy, we absolutely need things that can tell us who’s who.”

The answer is testing and Fleming said the earlier this is done, the better.

Sequencing the genome of a tumour that has been removed can even help several years down the track if cancer recurs after surgery.

Currently, genome sequencing is available in New Zealand from private providers for around $5000 to $6000. Fleming does not know if any DHBs are routinely sequencing an entire genome of a tumour as standard practice. 

Routine personalisation

Fleming is excited at winning the fellowship, describing it as one of the best to win in the country. 

Previously, his work has been based on genomic sequencing of 200 bowel cancer patients’ tumours. Through this, three biomarkers were identified as potentially being useful for predicting whether a patient would respond to immunotherapy. He’s also found another class of drugs could be used in tandem with immunotherapy to further improve results.

The $600,000 of funds from the fellowship, awarded over four years, will be used to fund his time to test whether he’s correct in the laboratory. 

If he’s right, the results could justify a clinical trial, and if the clinical trial shows he’s right, immune checkpoint inhibitors could be prescribed with more certainty, and possibly for more cancer types, and stages.

All this translates to better outcomes for patients. 

“We’re seeing numbers that suggest people would have died if they hadn’t got the drugs. We’re seeing big changes in survival rates. It’s not just bowel cancer, it’s lung cancer, melanoma.”

He said it could be time for a paradigm shift to personalised treatment and pointed to what are called basket trials in the United States. 

“The trials take people who have really bad cancers and sequence them straight away. Then take any drugs off the shelf which might help that cancer, irrespective of what cancer it is. So they’re doing the exact opposite of one-size-fit all.”

His advice to patients is to ask their doctor if their cancer has been fully characterised. 

"If you're a cancer patient you can pay right now to have your cancer sequenced. You can take that information along to your doctor and say, 'Will, this information help?' I think there's a good chance it could."

There are strict rules around who is eligible for treatment with drugs such as Keytruda, the most well-known immune checkpoint inhibitor, but having tests showing it's likely to be effective for your cancer could help getting a prescription, or being included in a clinical trial.

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