It was seeing his own grandfather go through treatment for bowel cancer that inspired Dr Arutha Kulasinghe to become a cancer researcher, but it was a crucial piece of funding that has propelled him to be one of the most sought-after researchers in the country.
Dr Kulasinghe who recently won Cure Cancer’s 2023 Researcher of the year award, completed a Bachelor of Science and Honours majoring in medical microbiology at the University of Pretoria (South Africa) before completing a PhD in the investigation of circulating tumour cells in head and neck cancers at the Queensland University of Technology.
Now considered a pioneer in what is known as spatial transcriptomics, a high-tech way to map out a tumour and all its cell interactions to inform clinicians of the best approaches for each patient, Arutha has contributed significantly to world first studies in lung cancer, head and neck cancer and Covid-19 and had his research work published 86 times.
Importantly Dr Kulasinghe attributes much of his success to the donors and supporters of the PA Research Foundation.
“PA Oncologist Ken O’Byrne identified in 2020 that there were lung cancer patients that did really well on immunotherapies and flagged that as a research project to us. It’s a global challenge, not just one where we would only help patients at the PA,” he said.
“Almost serendipitously at the time, we were in the early days of spatial profiling and trying to understand tumor microenvironments. Ken had patients that had done well on immunotherapy and some patients that did really poorly and didn't know how to identify these patients. We explored why by looking at the tumour microenvironment in a small cohort.
“The PA Research Foundation funded a proposal for that which gave us that initial boost of funds to be able to investigate. This was very early days of spatial, almost like the nuts and bolts of it and James Monkman in my team was developing it. It was nowhere near where we are today with spatial.
“We were trying to figure out how best to optimize the assay and understand the tissue. But the really neat bit was we were bringing the pathologists and immunologists from the PA in, and they were on board as well.
“That first study with the PA allowed us to optimize a lot of the workflows and to understand what are the tissue types that are compatible with this analysis and develop some of the analysis pipelines in the lab. We wrote that work up, published it, and it’s well cited now.
“We then went into some of the large immunotherapy studies connecting the PA with some of the international cohorts from the U.S. and trying to really expand our research, it all started, with the funding from the Foundation.”
Spatial transcriptomics, described as a google maps approach to understanding the tumour microenvironment and what drives cancer growth, is now at the cutting edge of what is known as personalized medicine approaches. Personalised medicine refers to figuring out the best treatment for each individual patient to save them from unnecessary and ultimately unsuccessful treatment.
While this approach is still in a research phase, it is seen by many in the medical field as the future of cancer treatment. A biopsy would be taken from a patient, studied by a researcher like Arutha and a pathologist, whose work would then inform the clinician about what treatments offer the best chances of survival for the patient, be that immunotherapies, chemotherapy, hormone treatments etc.
Dr Kulasinghe and his team at the PA campus based Translational Research Institute are in heavy demand as their work can be applied to a range of solid tumours including head and neck, lung, prostate, breast cancer and more. Dr Kulasinghe reiterated that this wouldn’t have been possible without the Foundation.
“We've got a really cool technology and we need to keep optimizing assays, run them and try to understand the tissues. But where it's taken us over time is we can now understand each patient's tumour to a point where we can probably jump in a couple of years to larger clinical trials,” he said.
“What it's really enabled us to do is to stack the deck of information on lung cancers and expand it to head and neck and skin cancers. When investigators at the PA saw what we were doing in lung cancer they were excited because they see the same challenges in head and neck cancer, skin cancer and so on.
“The beauty of it is we are starting to identify the cellular neighbourhood by looking at the immune cells that are next to it, but also understanding the context of where it is. If we imagine a chemo cell as a house on a street or a number of houses on a street, we can essentially take a global overview of that. We can understand how the chemo cell is communicating with the immune cells neighbouring them and the different cell profiles, how they’re metabolically activated, whether pathways are activated etc.
“Why that's important is it tells us what are the signals that the tumor cells are turning on or off in response to the immune cells, that's important because that shapes how we give immunotherapies.
“That's where we are today. It was really enabled through that initial funding through the PA Research Foundation. If we took these proposals to national funding agencies, they wouldn't be interested because it's blue-sky type stuff where they would say no because there is not enough preliminary data.
“What the funding has done is set this foundation where look you've got an innovative idea, it's clinically relevant, let’s put a clinician and a scientist in a room together and get them to figure it out.”
Dr Kulasinghe said he sees spatial profiling playing a major role in the future of cancer treatment and being a key factor in saving lives.
“I think hopefully in the future where we’ll head to is treatment based on your individual tumor profile, you'll be given an individual therapy and if we know that there's metabolic markers increasing your tumor. We know that there's immune infiltration. We just need to activate your tumor cells to detect and attack the tumor more aggressively,” he said.
“You might be given a specific therapy. Whereas in a patient that's completely different, who has a completely different profile, they might be given a different therapy. It's about individualising those therapies.
“Currently, cancer patients are treated sort of universally, you give the drug, you see if it works, if it doesn't, you change or you, if it is working, you can keep the patient on it until they develop resistance and then you give the next iteration of the drug until you run out of drug and the patient dies of that resistance.
What we're trying to do is individualize that therapy, so we have the best potential outcome in treating the patient's individual tumor, but also treating it with the right drug so that you don't develop resistance because if you knock out, 95% of a tumor with your first therapy and there is still 5% that's resisting, it’s that 5% that's going to kill you.
“It's trying to figure out how do we treat the 95% of the tumor, but also the 5% that's resistant.”
“We are getting closer and closer to understanding why is it that the same drug affects two patients completely differently which is really important because that means we are getting closer to knowing how to effectively treat the entire tumour and not have that 5% that’s resistant.”
- Dr Arutha Kulasinghe
