Targeting cancer

Developments in cancer treatments in recent years have been incredible. Of course, conventional therapy such as chemotherapy and radiotherapy are still used and continue to benefit patients. But new therapy options that are more focused on targeting the disease directly – like CAR T-cell therapies for acute leukaemia, which we just wouldn’t have imagined a decade or so ago – have revolutionised treatment.

We now see people with metastatic melanoma surviving their disease – actually being cured, or controlling it, because they’re being treated with immunotherapy that makes tumour cells “visible” to the patient’s own immune cells. This is incredible seeing a disease that used to be an absolute death sentence now curable for some patients.

What we’re now missing is a way to predict which patients will benefit the most from which treatments. If a patient gets the right treatment, it’s a gamechanger.

You might have a group of children who all have the same type of sarcoma, at the same stage of disease. The clinician is going to say okay, they’ve all got this, this is what we give these patients. A certain percentage will respond quite well – but a certain percentage will fail the treatment. At the moment, it’s virtually impossible to understand when the patient’s going to respond or not just from looking at base pathology.

But now there is enormous effort to integrate precision medicine into cancer care. The idea behind this is to tailor treatment for individual patients so that potentially effective drugs are used, while ineffective, often toxic, agents are avoided.

To date, precision medicine primarily involves genomic analysis of a patient’s tumour to identify abnormalities that can be matched to a therapy for the patient. Cancer biology is more complex than just the genome, and other cellular factors influence how a patient tumour will respond to therapy.

Testing the tumour cells for response to therapy in the lab has many challenges. We’ve been doing a lot of work on tumour organoids – growing tumours in the lab. Our idea is to get patient samples and grow these as a mini tumour in the laboratory, then put these mini tumours through testing using a battery of drugs and potential treatments, find the best ones, and feed that back. We can look forward to a whole level of data analysis and prediction analysis to try and find the right treatment for the right patient and doing it in a rapid way. Most current treatments are still empirical. Integrating these technologies, genomics and cell-based screening, with machine learning is going to be very exciting.

But there are more immediate challenges. Growing a tumour in the laboratory is actually not that hard – if you just want to grow them and study individual ones, fine. But it becomes a challenge when you want to do some high throughput drug screening to understand which drugs are going to work. You can’t do that if you’re getting the variability of manually producing these patient tumours or if you are growing them in an environment that differs substantially to that found in the body.

One way to overcome some of these challenges is to engineer materials that mimic the microenvironment that tumour cells grow in. Another advance that is required is to be able to produce the mini tumours in a high-throughput, accurate and reproducible way. Along with our colleagues at UNSW and Inventia Life Sciences, we have done exactly that by developing an award-winning bioprinter. The bioinks we use with the printer have been designed to mimic the microenvironment that tumour cells grow in. Through design of our bioinks, we can precisely control this environment and ask fundamental questions about what controls the growth of a tumour, and how does this impact response to therapy.

Our focus is on growing and expanding tumours in the lab that reflect the original patient sample. This then means we test the samples simultaneously for responses to numerous therapies and identify which drugs destroy the tumours. Ultimately, we want to translate this to the clinic and identify the right treatment for the right patient in a clinically relevant time frame. Success will mean we realise our vision to improve outcomes for patients with aggressive cancers.

I was always interested in science in high school, but back then there was no suggestion that I could go to university, even though I was a high-calibre student. I was even talked out of going beyond year 10, probably because of my Greek background – they probably thought I was going to get married, have a family and drop out. My career advisor said, “You can do a pathology technician certificate.”

I’d just turned 16 when I started my very first job, working in a lab doing brain and auditory research at the University of Sydney. And that was an “a-ha” moment, suddenly realising all these amazing opportunities – that you could do a university degree, you could get your honours, then do a PhD and do research. I was loving what I was doing and decided right then that as soon as I finished my pathology technician certificate I was going to enrol in a biomedical science degree, so I could potentially progress towards a PhD.

At 21, I was offered a position at the then brand-new Children’s Cancer Institute that was located at the Sydney Children’s Hospital in Randwick and next door to the children’s oncology ward. Just before I started my role, I was diagnosed with cancer.

There I am at the hospital with all these sick kids, and I fitted right in as I had a bald head myself as a result of aggressive treatment for my cancer. Despite my own journey the children with cancer inspired me each day. It was not lost on me that at 21 years old I had some understanding on what was going on, but for many children it must have been difficult. I met a lot of kids who didn’t make it – it did, and continues to, drive me to want to work and make a difference.

When I was going through my treatment, I used to have to spend seven days in hospital being infused with highly toxic drugs. I would be sick and home or hospital bound for two weeks, and I had five or six days where I was well, before I went through the whole cycle again. Since then some treatments have changed. It is often given as day treatments – people get their infusions and go home. Or they’re given their treatment in tablet forms. There’s a whole range of changes in the last 10 years – the development of new therapies is encouraging. With cancer being the number one cause of disease-related death in children in Australia, much more needs to be done. I’m very excited about the possibilities – we’re learning more and more about the disease and what’s going on. Hopefully we are going to get to the point where we can start targeting particular genes directly in cancer – that’s where nanotechnology comes in. With RNA technology, we can potentially focus on genes that are driving cancer growth or modulate the immune system to target cancer cells directly. There are exciting opportunities for different types of treatments. And this extends beyond cancer.