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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Email: [email protected]

Location: Sutton

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Email: [email protected]

Location: Sutton

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Phone: +44 20 8722 4361

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Phone: +44 20 3437 6118

Email: [email protected]

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Email: [email protected]

Location: Sutton

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Email: [email protected]

Location: Sutton

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Email: [email protected]

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Location: Sutton

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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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Email: [email protected]

Location: Sutton

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Email: [email protected]

Location: Sutton

Professor Louis Chesler's group have written 113 publications

Most recent new publication 4/2025

See all their publications

Vacancies in this group

Working in this group

Postdoctoral Training Fellow

  • Chelsea
  • Structural Biology
  • Salary Range: £45,600 - £55,000 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 7 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]

Higher Scientific Officer - Drug Discovery Biology, Centre for Protein Degradation

  • Sutton
  • Cancer Therapeutics
  • £39,805 - £49,023
  • Fixed term

We are seeking to recruit a Higher Scientific Officer within the Induced Proximity Therapeutics (IPT) Team in the ICR Centre for Protein Degradation to support our molecular glue and PROTAC drug discovery projects and expand induced proximity technology. The IPT team focuses on three main areas of research: Cancer target validation Screening, profiling and molecular mechanism of action of molecular glue and PROTAC degraders Novel E3 ligase biology and ligand discovery The successful candidate will work in a multidisciplinary team and play a key role in target validation, developing in vitro and cell-based assays, and pharmacological characterisation of novel molecular glue degraders and PROTACs, but may also contribute to other activities. About you The successful candidate: Will be a strong team player who is technically minded and passionate about science and cancer drug discovery Will hold a first degree, and preferably a PhD, in biological science or biochemistry Will have experience in cancer biology/target validation, genetic manipulation techniques, in vitro and cell-based assay development and pharmacological compound profiling Experience in targeted protein degradation will be a significant advantage. Department/Directorate Information This position will be based in the ICR's Centre for Protein Degradation, a part of the Centre for Cancer Drug Discovery (CCDD) specialising in developing novel drug modalities that re-wire tumour cells' signalling by targeted degradation of key oncogenic drivers. Our experienced biologists work closely with medicinal chemists, biophysicists, computational scientists, oncology specialists and physicians on discovering new medicines - molecular glue degraders and PROTACs - using innovative screening platforms and characterising their mechanisms of action, as well as expanding the repertoire of novel degradable drug targets and E3 ligases (enzymes that mediate protein degradation). Our research provides a nucleus for the academics and pharmaceutical industry to explore therapeutic potential of targeted protein degradation from laboratory hypothesis-testing to early clinical trials, for the benefit of cancer patients. What we offer A dynamic and supportive research environment in one of the successful academic cancer drug discovery centres in the UK Access to state-of-the-art facilities and professional development Collaboration with leading drug discovery and oncology scientist Competitive salary and pension To learn more about this role, please download the attached job pack. For informal inquiries, please contact Dr Agnieszka Konopacka, Group Leader, Induced Proximity Therapeutics, Centre for Protein Degradation via email: [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

07/05/25

Researchers at The Institute of Cancer Research, London, have uncovered a hidden weakness in some breast cancer tumours that could lead to smarter treatment decisions.

The RB1 gene

One of the body’s natural defences against cancer is a gene called RB1. This complex gene is involved in many processes that keep cells healthy. It also helps control how quickly cells grow and divide.

When this gene is altered or missing, which happens in many different types of cancer, this is generally associated with an aggressive form of cancer.

Now, researchers have discovered that some cancers behave as though RB1 is altered, despite having an unchanged version of the gene – widening the group of patients who could potentially benefit from drugs designed to treat RB1-mutated cancers.

The team, working in the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR), analysed over 10,000 tumour samples from over 30 cancer types.

By comparing cancers with and without RB1 alterations, the researchers noticed that tumours that looked normal under standard genetic tests were behaving just like RB1-defective cancers. They called these cancers ‘RBness’ cases.

The discovery could change treatment

Cancers with mutations or alterations in the RB1 gene are linked to poorer outcomes, but they are associated with a better response to chemotherapies. They are also associated with a poor response to CDK4/6 inhibitors

This new discovery reveals that the RBness cancers have similar characteristics to those seen in patients with RB1 mutations. This means spotting RBness could help tailor treatments more effectively, offering chemotherapy where it’s likely to help, and avoiding treatments that may not.

The researchers also found that RBness cancers share many of the same weaknesses as those with altered RB1 genes.

This means that drugs that are developed to target weaknesses in RB1-altered tumours could potentially also work in cancers with RBness – opening the door to new treatment options in the future.

Bringing the research into clinical practice

This discovery opens up exciting new possibilities for improving how we treat breast cancer, but more work is needed to bring it into clinical practice. The researchers now hope to validate these findings in larger, real-world clinical studies.

Ultimately, this research brings us one step closer to truly personalised breast cancer treatment – where each person gets the treatment that’s most likely to work for them.

Dr Syed Haider, study co-lead and Team Leader of the Breast Cancer Data Science Group at The Institute of Cancer Research, London said:

“While certain new treatment strategies have improved the management of aggressive breast cancers, there are still many patients facing poor outcomes. Our research has identified a new sub-group of patients who may benefit from drugs that are being designed for others. In the longer term, we hope to discover how these RBness cancers came about, which may unlock even more weak points in the cancer cells that can be targeted.”

Professor Chris Lord, study co-lead and Deputy Head of the Division of Breast Cancer Research, and Professor of Cancer Genomics at The Institute of Cancer Research, London said:

“We have developed a new biomarker to identify the patients whose cancers don’t have alterations in RB1, but who seem like they would benefit from the treatments for those which do. This can be used for breast cancers, but the next stage is to validate it in large clinical cohorts, to see if how successful it will be at guiding treatment options.”