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Treating head and neck cancer

Monday 01 February 2021

Researchers at the PA Hospital believe personalising the treatment of patients with oropharyngeal squamous cell carcinoma, may not only save lives but improve the quality of life of thousands of patients.

A form of Head and Neck cancer that develops at the back of the throat, oropharyngeal squamous cell carcinoma (OPSCC), diagnoses have shifted in the past decade, with more cases caused by the human papillomavirus (HPV) as opposed to smoking and drinking alcohol.

Highlighting the need for research is the fact that though cervical cancer (which is also caused by HPV) rates are dropping, cases of HPV positive OPSCC are rising.

The research project entitled; High-resolution mapping of oropharyngeal squamous cell carcinomas to allow personalisation of immunotherapies will map patient tumours through the use of a technology called spatial transcriptomics, to determine the best course of treatment and ideally easing the combination of immunotherapies to reduce the burden of the traditional approach.

Research team member Dr Jazmina Gonzalez-Cruz said the team's focus is on identifying why immunotherapies, which essentially reactivate a patient's natural immune responses to attack tumours work effectively for some patients and not others, because immunotherapies can help to deescalate the dosages used in traditional chemo-radiotherapy saving patients their detrimental side effects.

PA Research Foundation board chair Robert Bowen with Dr Jazmina Gonzalez-Cruz and research team colleague Professor Ben Panizza.

"Until now, cancer management has looked like a one for all approach, the standard treatment of these patients will consist of chemo-radiotherapy with or without surgery ," she said.

"The more we know about the biology of the processes between the natural immune responses of patients and how the tumours reacts to them, we start to understand that actually, maybe it's better to do these characterizations and then tailor therapies to the patient, and this type of disease.

"Because what would be better than your own soldiers fighting the war, right?

"But that also means we need to understand at which stage the patient's immune system is working. Sometimes what happens is the tumours are smart and look for strategies to escape these responses, we need to understand at which stage the tumour is hiding from the immune system and understand how the immune system can be reactivated and directed towards the tumour."

Using transcriptomics, the researchers will be able to take a sample of the patient's cancer and screen for thousands of genetic markers to profile each patient to then guide oncologists and clinicians on which therapies are most suitable for each individual.

A key long term outcome the team hopes will come from the project is reducing the number of patients who need radio-chemotherapy, which can greatly impact quality of life.

"As the radiation is happening in the throat, one of the side-effects is patients have problems with swallowing, and now we have patients that are younger, thus carrying these side-effects for a longer period of time," Dr Gonzalez-Cruz said.

"Some people need to change their diet completely, imagine all of the sudden you're in your 50s, and you're like, "Okay, now I only can eat a baby food or almost liquid type diets because I cannot swallow"."

"The program that we have right now with immunotherapies is very promising. Theoretically, it looks beautiful. It looks like, okay, we look at the immune system and we say, "Come on guys, get up, this is the tumour" and we've re-educated the immune system to fight.

"But the reality is that in the oropharyngeal patients, only 20% of the patients respond. That's a problem because we don't know why the 80% didn't respond. Because in theory, they should have. They had the right markers that we thought they should have, and they should have responded, but they didn't.

"We think that's because, we may be being too simplistic about the differences between patients, because the difference between tumours, is just maybe one, two different markers. Our hypothesis is that these multiparametric technologies would allow us to screen many more markers at the same time, and then we can relate that with treatment outcome.
"Ideally at some point, we'll have clear profiles of what a patient that responds to these immunotherapies looks like, and be able to say, "Okay, so for Peter to respond to therapy A should have equal XYZ characteristics"."

Dr Gonzalez-Cruz said she remains eternally grateful to the PA Research Foundation's supporters whose generosity made the project possible.

"To anyone who has supported this research, thank you so much for caring. As things are right now in science, we are nothing without support, we cannot help people without your support. That's the reality.

"Bringing new therapies and hope to cancer patients is absolutely about teamwork. From the person who has their hands on the research bench to the surgeon that's cutting the tumour or giving the right therapy, to the people who actually care enough to donate their time or their money, so we can make these ideas reality and translate them to something that people actually can use to save lives or improve quality of life."

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