Sarcoma Molecular Pathology Team

Professor Janet Shipley’s team is investigating ways to improve the treatment of patients with soft tissue sarcomas associated with poor clinical outcome.

Our current research is primarily focused on rhabdomyosarcomas and includes understanding aspects of epigenetic regulation of differentiation and the DNA damage response that may be targeted and incorporated into the treatment of these and other sarcomas.

Professor Janet Shipley

Group Leader:

Sarcoma Molecular Pathology, Computational Pathology and Integrative Genomics Professor Janet Shipley

Professor Janet Shipley is investigating ways to improve the treatment of patients with sarcomas that have a poor outcome.

Rhabdomyosarcoma (RMS)

RMS account for around 6% of all childhood cancers and are broadly divided into two main histological subgroups: alveolar and embryonal RMS. Around 70–80% of alveolar cases are associated with PAX3/FOXO1 or PAX7/FOXO1 gene fusions.

Our work has shown that fusion gene negative alveolar RMS are clinically and biologically more similar to embryonal cases than alveolar and patients with PAX3/FOXO1 positive tumours are associated with poorer outcome.

This has important implications for risk stratification that are being incorporated into the next clinical trial by the European paediatric Soft tissue sarcoma Study Group (EpSSG). In addition, we have identified a gene signature associated with poor prognosis in fusion gene negative RMS that will be prospectively validated.

To find new approaches to treat these high-risk sarcoma patients we are identifying and validating:

  • Molecular therapeutic targets and agents that are prioritised from a novel computational analyses of molecular and experimental data (in collaboration with Professor Bissan Al-Lazikani). These are then being tested in our preclinical models.
  • Epigenetic modifying enzymes that have effects on the differentiation status or DNA damage response of RMS cells. These include the histone demethylase KDM4 family that is linked to a drug discovery project (collaboration with Professor Julian Blagg) and the histone methyl transferase EZH2 which is part of the polycomb repressive complex 2 (in collaboration with Dr Zoe Walters). This research aims to discover novel strategies for differentiation therapy and ways to make sarcoma cells more sensitive to current treatments which damage DNA.

Other sarcomas

Our research investigations are extended to desmoplastic small round cell tumours, liposarcomas, Ewing sarcomas and through collaboration with Professor Chris Lord, synovial sarcomas.

We have close links with clinicians at the Royal Marsden NHS Foundation Trust (in the Children and Young People's Unit and the Sarcoma Unit), the National Cancer Research Institute (NCRI) Clinical Studies Young Onset Sarcoma Subgroup (YOSS) and the European paediatric Soft tissue sarcoma Study Group (EpSSG).

These partnerships facilitate our research and take forward research advances to potentially benefit patients.

Research Support

Support for our sarcoma research has come from:

  • Sarcoma UK
  • Children with Cancer UK
  • The Chris Lucas Trust
  • RobsARTTT
  • Great Ormond Street Hospital Charity
  • The Tom Bowdidge Foundation
  • Cancer Research UK
  • Wellcome Trust
  • Elin Rose Appeal
  • Kidscan
  • Children’s Cancer & Leukaemia Group
  • The Kelly Turner Foundation
  • Alice's Arc
  • Leah Rothwell
  • Charlie's Wish


The aim of the Sarcoma Molecular Pathology Group is to identify molecular biomarkers of high-risk sarcomas and therapeutic strategies that will improve the treatment of patients with these sarcomas.

Sarcomas are a heterogeneous group of mesenchymal tumours that frequently exhibit features of differentiating tissues such as striated skeletal muscle (rhabdomyosarcomas) and fat (liposarcoma). They may also have an undifferentiated appearance. Sarcomas account for approximately 15% of cancers in children and adolescents compared with 1% of cancer in adults and are associated with considerable morbidity and mortality.

Our current research is primarily focused on rhabdomyosarcomas and includes understanding aspects of epigenetic regulation of differentiation and the DNA damage response that may be targeted and incorporated into the treatment of these and other sarcomas.

Previously, we have identified genes involved in testicular germ cell tumour development, including those that predict occult spread and relapse. Other research has led to the identification of rearranged genes, notably those involved in synovial sarcomas, chondrosarcomas, kidney carcinomas and a myeloproliferative disorder.

We have also derived genetic-based approaches to resolve diagnostic dilemmas for the differential diagnosis of small round cell tumours, synovial sarcoma and tumours of germ cell origin. More recently, we demonstrated that the PAX3-FOXO1 fusion gene, rather than alveolar histology, is a key prognostic marker with utility to stratify treatment for rhabdomyosarcoma patients.

Recent discoveries from this group

19/07/21

3D tumour spheroids of an aggressive soft tissue sarcoma, Desmoplastic Small Round Cell Tumours

Image: 3D tumour spheroids of an aggressive soft tissue sarcoma

Sarcomas occur all around the body in the bones, or in the soft tissues such as muscle, fat and blood vessels. They are hard to understand and treat. This is partly because there are around 100 different types which are biologically complex, researchers have fewer patients to study and funding is scarce. Sarcomas are also often diagnosed late, and patients have few treatment options meaning survival rates are poor. In over half of these patients, the disease spreads to other organs, at which point it is incurable. Many of the drugs prescribed today are the same as those approved decades ago and clinicians have had limited success with a ‘one-size-fits-all’ approach using chemotherapy. Sarcoma patients need more personalised treatments, tailored more closely to their individual tumours.

Our scientists are finding innovative ways to tackle the scientific, clinical and financial challenges of researching sarcomas. They are drawing from the expertise of their colleagues and building connections with other sarcoma researchers around the world. These networks are enabling them to recruit patients for clinical trials and pool resources like data, tissue samples and funding in ways that simply wouldn’t have been possible separately.

Rising to the challenge

Dr Paul HuangOne of the researchers leading the way is Dr Paul Huang, Leader of the Molecular and Systems Oncology Team. Dr Huang’s team characterises sarcomas on the basis of their molecular and genetic features to understand why patients respond differently to treatment and to identify new options for treatments.

Dr Huang’s team are searching for new biomarkers – biological features within our cells that can be measured and used to better understand individual cancers. Biomarkers can indicate whether a patient is likely to respond to a treatment, or how well a treatment is working for a patient. Dr Huang has recently identified a selection of biomarkers – a biomarker panel – that could be used to identify treatments for several types of sarcoma.

Dr Huang says: “There is so much that is still unknown about sarcomas compared to more common cancers. This can be daunting, but as a scientist it’s also very exciting because our research could unlock the underlying biology, which could then help us to identify new treatments.”

People with cancers of unmet need urgently require new treatment options to help them survive their disease. Improving the outlook for these patients is one of our key fundraising priorities. 

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A ‘symbiotic’ partnership

Dr Robin JonesTo connect his lab to the clinic, Dr Huang works closely with Professor Robin Jones, Head of the Sarcoma Unit at The Royal Marsden NHS Foundation Trust, and Team Leader in Sarcoma Clinical Trials at the ICR.

They describe their partnership as ‘symbiotic’. Professor Jones’ insights on clinical questions inform Dr Huang’s lab work. The two work closely together to identify new biomarkers, establish new clinical trials and develop new treatments. They draw on each other’s complementary knowledge, connections to pharmaceutical companies and links with other sarcoma researchers to advance their work.

Their partnership has helped lead to the development of a new Joint Sarcoma Research Centre at the ICR and The Royal Marsden. Professor Jones is co-Director alongside the ICR’s Professor Janet Shipley, who leads on childhood sarcoma research.

Encompassing all sarcoma-related research across the two organisations, the centre is one of the largest sarcoma research centres in Europe, and uniquely collaborative around this collection of cancers. The centre aims to build an international digital hub of clinical and research data on sarcomas. New collaborations have allowed the centre to source tissue donations and host visiting research fellows from around the world.

A key focus for the centre is the use of artificial intelligence to find targets for new drugs, and to predict how patients will respond to particular treatments. By analysing data across multiple sarcomas, it is also possible to find treatments that could work for several different types.

Future ambitions

Dr Huang is now working to develop tests that could help predict how individual patients will respond to treatments and identify new therapies that may be better tailored to their age, sarcoma site and genetic profile.

Our scientists have made great strides: they have identified biomarkers for better selection of targeted therapies, developed drugs from first in human studies through to larger later phase trials, and built networks to unite the international research community. Sarcoma research has lagged behind other cancers for decades and more support is needed to accelerate discoveries, to help transform the lives of sarcoma patients sooner.

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