Searching for the secrets of cancer super-survivors

This article featured in Illuminate Newsletter Winter ‘23

“I’ve had three different kinds of cancer and I’m still alive! What’s different about me?” That’s a question a small group of cancer “super-survivors” find themselves asking, and to which a team of researchers coordinated by WEHI’s Dr Kristy Shield-Artin and Professor Clare Scott AM is seeking answers.

People who develop three or more different primary cancers in their lifetime surprisingly seem to have life expectancies close to those of the general population.

“These patients have either been incredibly lucky or – more likely – there’s some mechanism at work in these individuals that slows down and controls cancer progression,” says Dr Shield-Artin, a Senior Research Officer in the ACRF Cancer Biology and Stem Cells division.

“Understandably, we’re very interested in identifying that mechanism.”

National research project

The multiple primary cancer project began in 2016 as an intriguing clinical observation by Prof Scott, as part of the work of her team in building the national WEHI Stafford Fox Rare Cancer Program, supported by the Stafford Fox Medical Research Foundation.

This super-survivor program is now a national initiative that involves several institutes and researchers.

“Over a seven-year period, we’ve identified 32 patients from around Australia, diagnosed with three or more different cancers in their lifetime,” says Dr Shield-Artin.

“It’s a unique group, encompassing 40 different tumour types and over 100 tumour samples. “Each of them has had at least one rare cancer – defined as a cancer with an incidence of fewer than six cases per 100,000 Australians per year – as well as two or more other types of cancer.”

Identifying whether these patients share a predisposition to cancer or their immune systems have special properties that have helped them overcome their cancers – or a combination of both – has implications for the diagnosis, treatment and even prevention of cancers in a much broader population.

Host response may be key

At the core of the project are tissue samples from cancers removed at surgery and a biobank of specimens from individuals with a rare cancer, established as part of the WEHI-Stafford Fox Rare Cancer Program.

“We’ve also initiated collaborations with other groups who have access to tissue from similar patients to enlarge our cohort,” says Dr Shield-Artin.

“We’re particularly interested in taking a close look at the immune responses of these patients to their different cancers, as this may be part of the explanation.”

Tissue samples are now being subjected to multiple layers of analysis. But the very small number of patients, as well as the need to look in great depth at both the genetics of different tumour types and the responses of patients’ immune systems, initially made it difficult to attract conventional research funding.

Fortunately, since 2020 the project has been funded by a Venture Grant from the Cancer Council of Victoria (CCV) for “high risk, high reward” cancer research; support Dr Shield-Artin says is ideally suited to the exploratory approach needed.

“The Venture Grant from CCV has allowed us to push ahead on a ‘blue sky’ project like this.

“There’s no guarantee of success, but if it does succeed it would be a significant advance in our understanding that could benefit many people.”

The grant also cemented a strong collaboration with the immunology group at RMIT University led by Distinguished Professor Magdalena Plebanski, demonstrating the importance of collaboration when addressing big questions. Importantly, work on the Venture Grant has also enabled the researchers to attract subsequent funding from the National Health and Medical Research Council.

Dr Justin Bedő and Dr Kristy Shield-Artin
Dr Justin Bedő and Dr Kristy Shield-Artin

Computer modelling

Dr Justin Bedő is the Stafford Fox Centenary Fellow in Bioinformatics and Computational Biology at WEHI and a key member of the project team.

“Once all the tissue samples from the patients have been processed and the genetic sequences of their different tumours determined, it’s my job to extract all the information I can from the data,” says Dr Bedő, whose expertise is in computer science and machine learning.

“Cancer cells typically have numerous mutations in their DNA.

“Once we know what mutations are present in a particular cancer cell, we use computer models to infer which of those mutations might lead to a change in cell surface proteins that makes them detectable by the immune system.”

Other members of the computational biology team working on the project include Dr Matt Wakefield, Jocelyn Penington and Professor Tony Papenfuss.

Having had cancer three times over is an incredibly challenging experience for anyone. But Dr Shield-Artin says the fact they have survived usually means patients are focused on understanding what has gone right, rather than what’s gone wrong.

She and her colleagues are aiming to have some initial clues about that by the end of this year.

“If there is something really special about them, they’re the living proof of it… and we want to know what it is!”

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First published on 01 June 2023
This article featured in Illuminate Newsletter Winter ‘23
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