What if you could save somebody from complex surgery and grueling radiotherapy to treat their cancer, by understanding what is driving their cancer growth and then potentially halting that growth using immunotherapy?
This is the question driving the research of PA Hospital (PAH) based head and neck cancer clinician and researcher Dr Jonathan Helena.
Thanks to funding from the PA Research Foundation, the project, which is the clinician’s first ever funded study, involves using proteomics (study of proteins) to examine what’s known as perineural spread. Perineural spread is a condition when squamous cell carcinomas (SCC) or other skin cancers spread to deeper tissues and infiltrate large nerves.
The study is a collaboration between the PAH’s Head and Neck and Skull Base Surgery Unit , PA Department of Anatomical Pathology ( Dr Duncan Lambie ) and the ProCan team led by Children’s Medical Research Institute’s Professor Phil Robinson.
Current treatment for perineural spread often involves complex surgery followed by radiation. For some patients this isn’t successful, but immunotherapy offers hope.
“The head and neck region has a large density of nerve fibers; their role is to provide sensation and coordinate motor functions like facial expression. What can happen is the cancer can spread even after it’s been cut out. Tumour cells can infiltrate nerves, spread directly to the brain which becomes a challenging problem to treat,” Dr Helena said.
“Some patients demonstrate treatment resistance. Some of them have gone on to an immunotherapy trial led by PA’s Associate Professor Rahul Ladwa and have had promising results”.
“A lot of work has been done with genetic studies, looking at genes and the genetic profile of tumors to help us understand or predict how tumors will grow, or predict if a patient will respond to treatment. The thing with genes is they only tell us a part of the story. From genes we get peptides and proteins and that’s what gives us a fuller picture”.
“PA’s Professor Ben Panizza and Dr Chris Jackson have recently applied proteomics to look at HPV Positive Oropharyngeal cancers. What they’ve done is look at protein markers to try and determine which patients are likely to respond to treatment and which patients aren’t. That same technology is now being applied to cutaneous head and neck SCC and we want to answer similar questions.”
The multifaceted study entitled; Application of proteomics to predict the development of perineural spread in cHNSCC and define the molecular mechanisms that drive aggressive tumour biology, hopes to unlock the mystery around why patients develop perineural spread. In doing so it will also help in understanding which patients aren’t likely to respond to surgery and radiotherapy so they can be treated with alternative modalities like immunotherapy.
“We want to look at what the protein makeup is and compare it to other squamous cell carcinomas in the head and neck region that don’t develop perineural spread. We will look at the differences in the proteins to understand why,” Dr Helena said.
“We’re trying to understand the molecular mechanisms that initiate and drive perineural spread, there is research out there and different hypotheses, but nothing’s been confirmed. This is something that will give us more concrete answers to understand the mechanisms that drive the tumour biology. In addition, we want to be able to predict which SCC lesions will go onto develop perineural spread.
“The other component is a lot of these patients with perineural spread require extensive surgery and we want to analyze that tumour.
“We want to know which patients are likely to improve and respond to current treatment and which patients are likely to not do well. By stratifying patients early, we can give them the best treatment based on the outcomes of their tumour profile. Some patients do very well on checkpoint inhibitor immunotherapy and by looking at the proteins we can know which patients will do well on adjunctive immunotherapy like this.
“It may save patients from going through extensive surgery and radiotherapy in the future.”
Having himself benefitted from cochlear implants, which has allowed him to chase his passion for surgery. Jonathan has a natural affinity for the ENT field and added though he has worked in other disciplines he enjoys the complexity of ENT surgery and the breadth of patients they serve.
“I’m grateful for the funding from the Foundation, and to be affiliated with the PA’s head and neck research unit. Prof Panizza has established a very proactive clinical and research culture which is all about improving outcomes for patients,” he said.
“PA is the leading center for the management of this disease. Queensland is the skin cancer capital of the world, and we get a lot of referrals from all over the state like Cairns, Townsville, and the Gold Coast. It’s the place to be if you want to make a difference for these patients.”
