Paediatric Solid Tumour Biology and Therapeutics Group

Professor Louis Chesler’s group is investigating the genetic causes for the childhood cancers, neuroblastoma, medulloblastoma and rhabdomyosarcoma. 

Research, projects and publications in this group

Our group's aim is to improve the treatment and survival of children with neuroblastoma, medulloblastoma and rhabdomyosarcoma.

The goal of our laboratory is to improve the treatment and survival of children with neuroblastoma, medulloblastoma and rhabdomyosarcoma, three paediatric solid tumours in which high-risk patient cohorts can be defined by alterations in a single oncogene. We focus on the role of the MYCN oncogene, since aberrant expression of MYCNis very significantly associated with high-risk in all three diseases and implies that they may have a common cell-of-origin.

Elucidating the molecular signalling pathways that control expression of the MYCN oncoprotein and targeting these pathways with novel therapeutics is a major goal of the laboratory. We use a variety of innovative preclinical drug development platforms for this purpose.

Technologically, we focus on genetically engineered cancer models incorporating novel imaging (optical and fluorescent) modalities that can be used as markers to monitor disease progression and therapeutic response.

Our group has several key objectives:

  • Mechanistically dissect the role of the MYCN oncogene, and other key oncogenic driver genes in poor-outcome paediatric solid tumours (neuroblastoma, medulloblastoma, rhabdomyosarcoma).
  • Develop novel therapeutics targeting MYCN oncoproteins and other key oncogenic drivers
  • Develop improved genetic cancer models dually useful for studies of oncogenesis and preclinical development of novel therapeutics.
  • Use such models to develop and functionally validate optical imaging modalities useful as surrogate markers of tumour progression in paediatric cancer.

Professor Louis Chesler

Clinical Senior Lecturer/Group Leader:

Paediatric Solid Tumour Biology and Therapeutics Professor Louis Chesler (Profile pic)

Professor Louis Chesler is working to understand the biology of children’s cancers and use that information to discover and develop new personalised approaches to cancer treatment. His work focuses on improving the understanding of the role of the MYCN oncogene.

Researchers in this group

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Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6124

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OrcID: 0000-0003-3977-7020

Phone: +44 20 3437 6109

Email: [email protected]

Location: Sutton

I obtained an MSci in Biochemistry from the University of Glasgow in 2018. In October 2018 I joined the labs of Dr Michael Hubank and Professor Andrea Sottoriva to investigate the use of liquid biopsy to monitor clonal frequency and emergence of resistance mutations in paediatric cancers.

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Email: [email protected]

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Location: Sutton

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Professor Louis Chesler's group have written 112 publications

Most recent new publication 1/2025

See all their publications

Vacancies in this group

Working in this group

Head of Biology and Director, Centre for Target Validation (Group Leader)

  • Sutton
  • Cancer Therapeutics
  • Competitive Starting Salary
  • Permanent

Under the leadership of Dr Olivia Rossanese, we are seeking to appoint a Team Leader to join The Centre for Cancer Drug Discovery (CCDD) as The Head of Biology and Director of the Centre for Target Validation. Key Requirements The successful candidate must have in-depth knowledge and recent experience in an area of cancer biology relevant to oncology drug discovery. Leadership experience of drug discovery within, or in collaboration with, the pharmaceutical or biotechnology industry as evidenced by publication and/or successful commercial projects. Along with completing the online application form, you will be asked to attach the following documents and failure to do so will mean your application cannot be considered on this occasion: · Full CV · Lists of major publications, achievements, research grants, distinctions. · A PDF of a maximum of five key publications, or other research outputs (e.g. patents) that best demonstrate previous productivity · You must also complete the personal statement section of the application form in the format of a covering letter including the names and contact details of three academic referees Department/Directorate Information: The Division of Cancer Therapeutic's mission is to develop personalised medicines by translating information from the cancer genome and cancer biology into drugs for patient benefit. We implement innovative drug discovery technologies, discover novel mechanism-based drugs, and develop these as rapidly as possible from the laboratory through to hypothesis-testing early clinical trials We encourage all applicants to access the job pack attached for more detailed information regarding this role. For an informal discussion regarding the role, please contact Dr Olivia Rossanese, Email [email protected]

Postdoctoral Training Fellow

  • Chelsea
  • Structural Biology
  • Salary Range: £38,700 - £45,500 per annum
  • Fixed term

Under the leadership of Claudio Alfieri, we are seeking to appoint a Postdoctoral Training Fellow to join the Molecular Mechanisms of Cell Cycle Regulation Group at the Chester Beatty Laboratories, Fulham Road in London. This project aims to investigate the molecular mechanisms of cell cycle regulation by macromolecular complexes involved in cell proliferation decisions, by combining genome engineering, proteomics and in situ structural biology. For general information on Post Doc's at The ICR can be found here. Key Requirements The successful candidate must have a PhD in cellular biochemistry and experience in Cryo-EM and CLEM is desirable. The ICR has a workforce agreement stating that Postdoctoral Training Fellows can only be employed for up to 7 years as PDTF at the ICR, providing total postdoctoral experience (including previous employment at this level elsewhere) does not exceed 10 years Department/Directorate Information: The candidate will work in the Molecular Mechanisms of Cell Cycle Regulation Group within the ICR Division of Structural Biology headed by Prof. Laurence Pearl and Prof. Sebastian Guettler. The division has state-of-the-art facilities for protein expression and biophysics/x-ray crystallography, in particular the Electron Microscopy Facility is equipped with a Glacios 200kV with Falcon 4i detector with Selectris energy filter and the ICR has access to Krios microscopes via eBIC and the LonCEM consortium. We encourage all applicants to access the job pack attached for more detailed information regarding this role. For an informal discussion regarding the role, please contact Claudio Alfieri via Email on [email protected]

Industrial partnership opportunities with this group

Opportunity: A novel test for predicting future cancer risk in patients with inflammatory bowel disease

Commissioner: Professor Trevor Graham

Recent discoveries from this group

18/02/25

Scientists have developed a simple blood test that will help them better understand children’s cancers - and pave the way for new targeted and less toxic treatments.

A team of researchers from the Institute of Cancer Research, London, have been trying to develop a less invasive way of tracking how childhood tumours adapt and change in response to treatment.

New findings of the Stratified Medicine Paediatrics (SMPaeds1) programme, published in the journal Cancer Discovery, have successfully demonstrated that circulating tumour DNA (ctDNA) testing can be used to give a more complete picture of how a tumour develops over time.

Studying how tumours adapt

During the study, the team looked at samples of childhood tumours at initial diagnosis and circulating tumour DNA - fragments of tumour DNA in the blood - at the time of relapse to see how tumours adapt and change in response to treatment.

In some patients, it could even detect additional DNA mutations that were missed by the original tumour biopsy. 

Since ctDNA testing only requires a blood sample from the patient, the procedure is much less invasive than a tumour biopsy which usually requires a general anaesthetic.

Understanding what drives relapse

It is hoped these findings will pave the way for better understanding of what drives relapse or lack of response to treatment, and with it the hope of developing better, more targeted treatments.

The project, which was funded by Children With Cancer UK and Cancer Research UK, is led by Professor Louis Chesler, Professor of Paediatric Cancer Biology at The Institute of Cancer Research, and Consultant in Paediatric Oncology at The Royal Marsden NHS Foundation Trust.

It builds on earlier research at the ICR made possible by the parent-led charities Christopher’s Smile, Aoife’s Bubbles and Abbie’s Fund.  

The second phase of the research programme (SMPaeds2) also co-funded by Children with Cancer UK and Cancer Research UK, is currently underway and aims to further develop and study new tests that will build upon the success of the first phase of the programme.

Developing tests for clinical use

SMPaeds2 will investigate blood cancers and solid tumours in children and young people, including cancers of the brain, muscle and bone, which can be more difficult to access, diagnose and treat. 

Study author Dr Sally George, Group Leader of the Developmental Oncology group at the Institute of Cancer Research, London and an Honorary Consultant Paediatric Oncologist at The Royal Marsden NHS Foundation Trust, said:

 “We showed that ctDNA analysis can add valuable information and that in some patients it can detect additional DNA mutations that are in the tumour but were missed by tumour biopsy.” 

 “SMPaeds1 is the largest study with matched ctDNA and tissue sequencing to date and shows the value of ctDNA testing for children with cancer. We are working with colleagues across Europe to transition ctDNA analysis from being a research test to being available clinically.  
 
“The project also identifies DNA mutations that become enriched at relapse. This will help us prioritise future research to understand why those mutations are enriched and if we can develop new treatments to target cancers with those mutations.” 

Children with Cancer UK CEO, Amar Naher said:

“We’re proud to be involved in a research project leading the way in advancing precision medicine in the UK. Children with Cancer UK's mission is to create a world where every child and young person survives their cancer diagnosis.

“We strive to meet this mission through funding impactful research. The outcomes from the SMPaeds programmes could help in the development of targeted treatments and could lead to improved, less invasive ways of monitoring and treating childhood cancers.

“By identifying genetic changes that drive relapse, the project helps advance personalised treatments, supporting the charity’s aims to improve survival rates and quality of life for young cancer patients.” 

‘This research is unlocking new ways to study and treat childhood cancers’

Dr Laura Danielson, children’s and young people’s research lead at Cancer Research UK, said:

“We’re excited about this new research from the SMPaeds programme revealing the potential use of less invasive blood tests to better understand solid tumours in children and young people.

“These data demonstrating that analysing ctDNA could lead to a more complete picture of the tumour and how it is changing over time are incredibly important. This will pave the way for better understanding of what drives relapse or lack of response to treatment, and with it the hope of developing better, more targeted treatments.

“We're proud to fund innovative research like this, which is unlocking new ways to study and potentially treat childhood cancers to give young cancer patients the best possible chance to live long, healthy lives."