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

Email: [email protected]

Location: Sutton

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Location: Sutton

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Phone: +44 20 3437 3617

Email: [email protected]

Location: Sutton

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Phone: +44 20 8722 4186

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 3501

Email: [email protected]

Location: Sutton

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Email: [email protected]

Location: Sutton

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Phone: +44 20 8722 4361

Email: [email protected]

Location: Sutton

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Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6118

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6021

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6196

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6258

Email: [email protected]

Location: Sutton

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Email: [email protected]

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Email: [email protected]

Location: Sutton

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Phone: +44 20 8722 4527

Email: [email protected]

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]

Location: Sutton

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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 112 publications

Most recent new publication 1/2025

See all their publications

Vacancies in this group

Working in this group

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]

Postdoctoral Training Fellow – X-Ray Crystallography

  • Sutton
  • Hit Discovery & Structural Design
  • £45,600 - £51,450
  • Fixed term

A postdoctoral position is available in Dr Rob van Montfort’s Hit Discovery and Structural Design Team within the CCDD. The Post-doc will be involved in the structure determination of protein-ligand complexes, primarily by X-ray crystallography but also potentially by cryo-electron microscopy (cryoEM), as part of one of the CCDD’s drug discovery programmes. The postholder will be responsible for protein production and purification, protein crystallisation, structure determination by X-ray crystallography and subsequent structural analysis. The successful candidate will be an integral member of a multidisciplinary project team within the CCDD at the ICR Sutton site, and will interact closely with biologists, computational chemists, medicinal chemists, assay scientists and structural biologists.They will have access to state-of-the-art facilities for protein production and purification, as well as biophysical characterisation and crystallisation at the Sutton site. We also benefit from excellent access to Diamond Light Source synchrotron at the Harwell Science and Innovation campus, Didcot, UK, for X-ray data collection. Additionally, the successful candidate will also be part of the Division of Structural Biology, located in Chelsea, in which the structural biologists in Dr van Montfort’s team are also embedded, and will have access to its state-of-the art cryoEM facilities. These include an in-house Glacios and 30% direct access to a Titan KRIOS located at the Francis Crick Institute. Both microscopes are equipped with Falcon III detectors and volta phase plates (VPP). In addition, we have excellent access to the electron bioimaging Centre (eBIC) at the Harwell Science and Innovation campus, Didcot, UK. About you The successful candidate must have must have a PhD (or equivalent) in a biological or physical science, with demonstrable experience in X-ray crystallography and protein biochemistry. Experience in cryo-EM specimen preparation and data processing would be an advantage, though not strictly mandatory. Experience in molecular biology, protein expression and purification, as well as biophysical characterisation of protein samples would also be highly desirable. The ICR has a workforce agreement stating that Postdoctoral Training Fellows can only be employed for up to 7 years as PDTF (including previous employment at this level elsewhere). For general information on Postdocs at The ICR, more information can be found here. Department/Directorate Information The Institute of Cancer Research (ICR), London, is one of the world’s most influential cancer research institutes, with an outstanding record of achievements dating back more than 100 years. We provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today, the ICR leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment. Together with our hospital partner The Royal Marsden, we are rated in the top four centres for cancer research and treatment worldwide. As well as being a world-class institute, we are a college of the University of London. We came top in the league table of university research quality compiled from the Research Excellence Framework in 2014 and second in 2021 (REF 2014 and 2021). The ICR is committed to attracting, developing and retaining the best minds in the world to join us in our mission – to make the discoveries that defeat cancer. Department/Directorate Information: The Centre for Cancer Drug Discovery (CCDD), within the Division of Cancer Therapeutics, is a multidisciplinary 'bench to bedside' centre, comprising around 160 staff dedicated to the discovery and development of novel therapeutics for the treatment of cancer. The CCDD’s exciting goal is to discover high quality small molecule drug candidates and to progress these to clinical trial. All the scientific disciplines are in place to make this possible, including medicinal chemistry, biology, structural biology, assay scientists, drug metabolism and clinical specialists. This is an exciting and fast-moving research setup and offers the opportunity to work within a multi-disciplinary environment using state-of-the-art techniques and equipment. What we offer A dynamic and supportive research environment Access to state-of-the-art facilities and professional development opportunities Collaboration with leading researchers in the field Competitive salary and pension 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 van Montfort [email protected] or Dr Le Bihan [email protected]. Please DO NOT send your application to Dr Van Montfort or Dr Le Bihan, but apply via the e-recruitment system on our websitewww.icr.ac.uk/careers.

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

05/03/25

Researchers have uncovered several biological signs that may determine how metastatic castration-resistant prostate cancer (mCRPC) responds to a new treatment combination. The scientists made these discoveries as part of a phase III mCRPC trial investigating the effects of adding the drug ipatasertib to abiraterone, the standard of care.

Using a powerful sequencing technique to analyse tumour samples, the team showed that the addition of ipatasertib, an AKT inhibitor, helped certain groups of mCRPC patients – those whose cancer had specific genetic alterations – survive longer without the disease progressing. However, other patients did not benefit.

This knowledge could be used to help ensure that patients who are likely to benefit from the combination therapy receive it while others are spared unnecessary additional medication.

The study findings may also lead to new treatments for prostate cancer, as the identification of tumour genomic alterations associated with greater benefits revealed a biological pathway that researchers are now targeting in drug development work. Better treatment options are urgently needed for this condition, as the aggressive nature of the prostate cancer subtypes with these targeted alterations means that outcomes are generally poor.

Professor Johann de Bono, Head of the Division of Clinical Studies at The Institute of Cancer Research, London, was first author on the paper, which was published in the journal European Urology. The research was funded by Roche.

Outcomes are not consistent across the patient population

The trial, called IPATential150, enrolled 1,101 patients with previously untreated mCRPC. All of the participants received abiraterone, but while half of them received ipatasertib alongside it, the others were given a placebo instead.

Abiraterone, which was designed and developed at The Institute of Cancer Research (ICR), works by stopping the body from making testosterone, which prostate cancer uses to grow. Ipatasertib has a different mode of action, blocking the activity of a protein called AKT to inhibit cell proliferation and migration.

Overall, the addition of ipatasertib to the treatment regimen did not have a significant effect on the participants’ survival. At a median follow-up of 33.9 months, the median overall survival was only slightly longer in the ipatasertib group than in the placebo group – 39.4 months compared with 36.5 months.

However, when the researchers looked more closely at the most common genetic alterations across the patients’ tumour samples, they were able to associate certain characteristics with better or worse outcomes.

The importance of genetics

Of primary interest was the loss of PTEN gene function, which affects almost half of mCRPC patients and can occur due to genomic deletions or rearrangements. This gene suppresses the AKT signalling pathway that is often overactive in prostate cancer. The pathway regulates cell growth, survival and metabolism, and when dysregulated, it can promote the progression of the disease. Given that ipatasertib affects this pathway, the team were keen to see whether its addition to the treatment regimen led to better outcomes for this group of patients.

The researchers also investigated the PIK3CA/AKT1/PTEN pathway, which is known to be a major signalling pathway in multiple types of cancer. It has roles in controlling the survival and spread of cancer, as well as in managing the tumour environment. Analysis of the patients’ tumour samples revealed that the PIK3CA/AKT1/PTEN pathway was altered in 34 per cent of cases.

When the researchers compared the groups of patients with PTEN loss or PIK3CA/AKT1/PTEN pathway alterations with the other participants, they found that the addition of ipatasertib to abiraterone increased median overall survival by a more notable amount – from 29.2 months to 37.1 months.

This suggests that people whose tumours have these characteristics are likely to benefit from the ipatasertib-abiraterone combination treatment. This approach is not yet approved for clinical use, but the current research provides convincing evidence to support its use as a standard of care for certain patients.

Further research on the PIK3CA/AKT1/PTEN could also lead to new targeted medications that improve outcomes for more people with mCRPC.

“There is an urgent need for new treatments that improve outcomes”

Professor Johann de Bono, Regius Professor of Cancer Research and a Professor in Experimental Cancer Medicine at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust, said:

“Many different genes can play a part in the development and progression of mCRPC, and the genetic changes across cells within the same tumour can be very diverse. As a result, patients typically develop treatment-resistant disease that is difficult to treat. There is an urgent need for new treatments that improve outcomes in these aggressive subtypes of prostate cancer.

“We are pleased that this trial – the first phase III trial of an AKT inhibitor, ipatasertib, with abiraterone in this type of prostate cancer – has uncovered new biomarkers that could help identify the patients most likely to benefit from this combination treatment.

“Further trials are needed to identify other groups of patients who may find this approach effective, but based on our findings, we believe that it could benefit about 12,000 people a year in the UK alone. The number of years of life saved could be extraordinary."