Developing personalised treatment for ALK-positive neuroblastoma

Perla Pucci in the laboratory

Thanks to funding from Neuroblastoma UK, post-doctoral research associate Dr Perla Pucci was recruited to join a neuroblastoma research team at the University of Cambridge.

The team, led by Dr Suzanne Turner, are looking to develop more personalised treatment for children with ALK-positive neuroblastoma.

Perla tells us more about how the project has progressed since receiving £236,141 as part of our 2019 grant round.

Can you tell us more about your research?

I work in Professor Suzanne Turner`s laboratory as a postdoctoral research associate. I’m involved in an exciting project to develop personalised therapies to prevent and treat Anaplastic Lymphoma Kinase (ALK)-positive neuroblastoma, resistant to ALK inhibition.

ALK is a gene that controls how and when nerve cells grow, divide and die. A mutation in this gene can activate other proteins in the tumour cells, leading to uncontrolled growth and cancer development.

The first decade of this millennium shed light on the oncogenic role of ALK in neuroblastoma and my team is researching on the roles of ALK in the treatment of neuroblastoma and other paediatric cancers.

When did you start on this project?

My role started in March 2020, at the same time as the beginning of the Covid pandemic.

It has been hard to work from home and gradually being able to go back to the laboratory for my main work. Our work and lives are still affected from these difficult times but thanks to this project we have been able to progress with this important research.

What research challenges have you faced during lockdown?

“Thanks to the opportunity given by Neuroblastoma UK and my supervisor Suzanne Turner, I have been able to progress into oncology research, even in these difficult times.”

The week after I started my new role in neuroblastoma research, the first lockdown began. It has been hard not to be able to interact with my team and collaborators, unless via a screen.

Since the first lockdown, we have been able to return to the laboratory for essential research but are facing several new challenges, such as shift work and reduced capacity so that we are socially distanced from one another.

Laboratory consumables, essential for our research, have also been supplied with reduced efficiency, due to the difficult times that everyone is facing.

Thanks to the opportunity given by Neuroblastoma UK and my supervisor Suzanne Turner, I have been able to progress into oncology research, even in these difficult times.

What do you hope to learn from your research?

I hope to learn which mechanisms drive resistance to ALK inhibition in neuroblastoma cells and preclinical models, that will have a significant impact on clinical trials and patient care in the near future.

Learning how to interact with and promote collaborations between experimental research labs and clinical practice will hugely improve our approaches to a new generation of personalised medicine.

Why are you interested in neuroblastoma research?

“...My long-term goal is to develop targeted combination therapies, which could improve not just children’s survival but also the quality of their lives...”

I have always been fascinated about the molecular mechanisms that promote cancer progression and aggressiveness and how to fight these processes.

With the advent of novel therapies aimed at overcoming drug resistance and improving outcomes for patients, unfortunately, increased drug resistance has been observed, leading to reduced quality of life and survival.

ALK inhibition in neuroblastoma has shown promising results but cancer cells can respond via bypassing this inhibition and turning-on other mechanisms to escape the treatment effect and become more aggressive.

My long-term goal is to develop targeted combination therapies, which could improve not just children’s survival but also the quality of their lives, by a reduction in treatment administration and side effects.

What motivates you in your role?

“...My motivation comes from the passion for my work and the hope that one day the problem of cancer treatment resistance will be solved...”

My motivation comes from the passion for my work and the hope that one day the problem of cancer treatment resistance will be solved, with an efficient and successful collaboration between both the experimental laboratory research and the clinical practice, from bench to bedside.

I am passionate about molecular oncology, studying signalling pathways in cancer cells and their response to therapeutic stress, which can turn on even more aggressive responses, leading to tumour recurrence and ultimately, death, in the worst cases. ALK is a driver of oncogenic signals in different tumours, including non-small cell lung cancer and anaplastic large cell lymphoma, the latter of which is another paediatric malignancy.

By studying the molecular mechanisms that allow bypass of ALK inhibition, leading to treatment resistance, it will be possible to treat high-risk ALK-driven neuroblastoma and other aggressive ALK-driven tumours without fear of relapse, improving a child`s quality of life and saving lives.

What do you think the future holds for you and neuroblastoma research?

“...personalised treatments...can avoid these [long term side] effects and make cancer therapies successful. I hope this will be possible in the not so distant future.”

As an oncology researcher I hope that improving neuroblastoma treatment will reduce the short and long-term side effects of toxic drugs, which affect children’s lives, even in more easy to treat cases.

The development of novel targeted therapies and personalised treatments, based on patients’ molecular signature and their responses to specific therapies, can avoid these effects and make cancer therapies successful. I hope this will be possible in the not so distant future.