Discipline Hopping: Colorectal Cancer Therapy

Lead Research Organisation: University of Leeds
Department Name: Physics and Astronomy

Abstract

One in two people will have cancer during their lifetime. Cancer affects almost everyone whether it is friends, relatives, or the patient themselves. Over the last four decades, innovation in treatment has improved the outcome of many patients by extending life, improving quality of life, and even curing their cancer. However, 28% of all deaths in the UK are still due to cancer. Colorectal (or Bowel) cancer is the fourth most common cancer in the UK, with over 110 cases diagnosed per day. The best-known treatment is surgical removal of the tumour; however, there are challenges to this operation. For example, it is not always easy to remove the entire tumour and failure to do so leads to recurrence. An important clinical need is to improve the surgeon's ability to identify the tumour margins. The other main treatments include radiotherapy, chemotherapy, and immunotherapy. Unfortunately, they are not always successful and might only result in the extension of life or in the worse case have no measurable effect. It is widely recognised that difficult problems require a multidisciplinary approach. Creating new, more effective, cancer treatments is a big challenge, and almost all research funders (charities and research councils) recognise the benefits of multidisciplinary teams to find solutions. However, between the disciplines, there are knowledge gaps, which can slow down progress and lead to solutions to the wrong problems. In this proposed Healthcare Discipline Hopping Award, I will be learning, training, and researching all aspects of colorectal cancer treatment. This will give me the ability to build bridges between the disciplines. To do this I will be integrating with the clinical practice so that I can understand the diagnosis (screening, pathology, and imaging) and the treatment (surgery, radiotherapy, and ablation). I will attend the weekly clinical multidisciplinary colorectal cancer meetings, which decide the treatment plans for each patient. I will observe all of the different CRC surgical operations performed on patients, such as open, robotic, and laparoscopic. This will provide an opportunity to fully comprehend the unmet needs and challenges to surgery, such as determining the tumour margins. I will witness radiotherapy being performed and learn about the limitations and opportunities for further research. I will also find out more about early-stage clinical trials and how basic research is translated i.e. what data sets are required and what are the standards. I will learn about intraoperative ablation treatments and how these could be advanced in the future. I will have access to healthcare economic and healthcare technology assessment experts to obtain a complete picture of the challenges to not only developing new treatment methods but also recognising potential pitfalls from the early stages.

I will be integrating with on-going CRC research projects with clinical partners that are developing various strategies to investigate new treatments. By engaging with projects, I will be learning the key techniques used for in vitro and in vivo evaluation. To broaden my knowledge further, I have planned visits to other medical research centres in the UK, Canada and the Netherlands. Finally, there will be four focussed workshops that will look at the clinical needs of various CRC and other cancer treatments. Members of the groups will include patients, clinicians, scientists, engineers, and industry representatives. Going beyond this award, I will maintain the network of researchers that will be developed during the award.

Planned Impact

IIn the long term, cancer patients will receive the greatest benefit from this award. During the award, the ideas and collaborations needed to generate better treatments to improve patient outcomes will be seeded. I will be meeting patient groups and listening to their hopes and concerns and using this information to begin to formulate research ideas that will not only address unmet clinical needs but also consider the patient's needs. Specifically, developing better imaging techniques for surgery will improve the ability to remove the entire tumour and minimise recurrence. This will extend patients lives and provide them with the knowledge that the treatment has a greater probability of success. It is hoped that we can also create research programmes to develop new ways to enhance radiotherapy, and again improve patient outcomes by reducing, or eliminating, the amount of surgical intervention required; thus, improving quality of life, and increasing the life of the patient. Similarly, other treatments, such as photodynamic therapy after surgery, or laser ablation, could be further developed further for colorectal cancer patients. All of the interventions to extend lives and improve quality of life have a benefit to the patient's family members. The National Health Service will benefit in the long term because they will be able to better treat cancer patients. The cost of treating patients with chemotherapy drugs is necessary because it extends lives, but it is also a large strain on resources. Being able to improve treatments so that they are more effective will reduce overall treatment costs. The current average treatment for cost colorectal cancer (CRC) per patient ranges from £3.4k to £12.5k for stage 1 to stage 4, respectively. The UK spends more than £1.6b per year on CRC along, with the total for all cancers amounting to >£9.4b. Enhancing cancer treatments could save the NHS millions. Changes in practice, as a result of research, can have large cost savings while also improving the outcomes. Pharmaceutical and related industries that will benefit from research developments. They will develop products, for example, nanoparticles for enhancing cancer treatments. A relevant UK company for this is Nanoco. Some aspects of the fluorescence-guided concepts are highly relevant to Nanoco and therefore potentially generate jobs and wealth by expanding their products in this area. I will also be contributing to the initial stages of the collaboration with NH TherAguix. Being able to demonstrate enhanced radiotherapy in colorectal cancer would be an entirely new application for this company. If successful, with over 110 CRC patients diagnosed per day in the UK alone, this would amount to significant wealth generation. Students of medical and physical science backgrounds will benefit because they will receive training and experiences from both disciplines from as a result of the 'Hop'. This will include final year projects, but also the formal taught courses will be influenced by what I learn during this award. For example, when I teach Nanotechnology and Bionanoscience I will be introducing clinically relevant elements to provide context. This will help train the next generation of nanoscientists that wish to have an impact on medicine. Finally, I will also be running public engagement sessions throughout the year to inform and engage the public and school children about nanoscience and its application to medicine.
 
Description In collaboration with clinical and biomedical researchers we have developed a novel method of tracking the migration of cells into tissue models using a combination of fluorescence microscopy (acquired over days) and image processing to correct and determine the relative motions of cells (and their associated characteristics). This can be applied to cancer models and be used to follow the effect of therapeutics.
Secondly, we have developed gold nanosheets for diagnostic sensing and we are testing this for colorectal cancer biomarkers to track the effectiveness of a therapeutic. The work itself needs further funding to be exploited.
Exploitation Route The Cell tracking algorithm developed will be useful to others studying cell infiltration in tissue and this will be made publicly available when formally published. The collaboration of the use of Au nanosheets for diagnostic sensing with Sure Screen could be important for biomedical sensing. This will be developed further either through the KTP bid or by funding the research in another way. There are confidentiality agreements.
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description The hop award is all about improving knowledge and communication between medicine and the sciences. I have been able to engage in project and add the the knowledge from a science perspective, but also learn more about the methods employed in surgery. Through attending meeting with surgeons I have learnt a lot about the research they are performing and how this fits with my research. From this I have developed some collaborations such as image processing projects which I would not have got involved with before. I have learnt that the skills I have as a physicists are helpful beyond my knowledge of nanoparticles. I will be continuing to attend meetings with the medical groups and continue to develop more collaborations.
First Year Of Impact 2021
Sector Healthcare
Impact Types Societal

 
Description Model Cancer Cell Tracking 
Organisation University of Leeds
Department Leeds School of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed a computer programme for tracking fluorescent cells over long periods of time (days) travelling though a organoid. The aim of the project is to understand how cancer cells infiltrate healthy tissue. This could be important for future treatment methods. I have developed the code myself during the fellowship and we are preparing two manuscripts on the work. I have also developed some simulations to explain the observations. We aim to continue this work and increase the complexity. We now have a working unique cell tracking algorithm that tracks the motion of cells in a moving and growing organoid which will have wider importance.
Collaborator Contribution The group has provided the experimental data, performed the experiments, developed the organiod and spheriod models and performed the data collection. The PhD student has obtain a scholarship to continue the work (fully funded) which is funded by Leeds Hospitals Charity.
Impact The PhD student obatin funding from the Leeds Hospitals Trust. The work is multi-disaplinary and includes clintians, biologists, and physicists. Undergraduates have been trained in the tracking of objects using Open CV image analysis software.
Start Year 2021
 
Description Silicon quantum dots University of Bologna: Paola Ceroni 
Organisation University of Bologna
Country Italy 
Sector Academic/University 
PI Contribution Paola's PhD student took part in a 3 month placement in Leeds to work on a new type of quantum dots which could be used for medical imaging. This work helped establish a collaboration with Prof David Jayne (School of Medicine). I funded the visit and we are planning a publication in the comming months. We molecular targets and the medical problem that needs to be solved.
Collaborator Contribution The contributing partners developed the Si QD technology and also part funded the placement in Leeds.
Impact The initial reults have not yet been published. We are also writting a review article.
Start Year 2020
 
Description Thin Au NS 
Organisation University of Leeds
Department School of Physics and Astronomy
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been developing method of characterising and synthesising Au nano materials. I have contributed to supervision of PhDs and PDRAs in this research area. We now have made an application for a KTP award with a partner Sure Screen Diagnostic Ltd to develop lateral flow sensors using our AuNS as active sensing components in the place of the standard spherical NPs which are currently used. Preliminary studies have been performed by a PhD student and a Post doc who was funded by an Impact Acceleration Grant.
Collaborator Contribution We obtained an EPSRC Accelerator award to seek commercialisation of the research. We now have a KPT bid which is being assessed. The details of the bid are currently confidential. SureScreen are a UK based who can deliver on lateral flow tests for infections such as COVID-19. They are one of the few (or possibly the only) UK company that can produce every element of a lateral flow test kit and is therefore national very important.
Impact Training of members of staff in synthesis and characterisation of advanced nanomaterials (PDRA and PhD student)/ Training of undergraduate student in the fabrication of Au nanomaterials. The project is multidisciplinary involving biomedical science, colloidal science, nanoscience, physics, and chemistry
Start Year 2021
 
Description Photoacoustics and Photothermal treatment Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The meeting was intended to bring academics, industrialists and clinitians together to discuss the future of photoacoustic imaging and photothermal treatment. We had about 45 attendees and speakers from the USA, Germany, France, and UK over two half days. We had open dicussions and intend to write up the outcome of the meeting in the near future.
Year(s) Of Engagement Activity 2021