Surgery is the current standard treatment option for chondrosarcoma patients; however, for those where surgery is not an option or whose cancer has already spread, treatment options are extremely limited.

Chondrosarcomas typically contain mutations in the IDH1 and IDH2 genes, but inhibition of these mutations or their consequences using targeted drugs has only been successful in a subset of patients, implying that not all chondrosarcoma tumours are the same.

To develop effective therapies that are given to the right patients, a better understanding of what makes chondrosarcoma patients different from each other is needed.

A research project grant has been awarded to Dr Paul Huang at the Institute of Cancer Research, London, working in collaboration with Professor Judith Bovée at Leiden University, to gain a better understanding of the biology of chondrosarcoma and to identify new targeted drugs that could be used for the correct patients.

What does this research aim to achieve?

The team will study in detail the proteins found in samples from 120 chondrosarcoma patients and their associated clinical data to:

  • Identify specific patterns in proteins that are present or absent (protein signatures) in different samples
  • Determine if these patterns correlate with genetic mutations and whether they could be used to predict patient outcomes or response to treatment
  • Find specific proteins within these signatures that could be inhibited with targeted drugs.

CRISPR-Cas9 is an advanced genetic engineering technique that allows scientists to remove, add or alter sections of the DNA, hence modifying genes in the laboratory.

The researchers will utilise this technique to manipulate the genes in chondrosarcoma cells and determine if the proteins these cells produce reflect the protein signatures observed.

The cells will then be grown in the laboratory to determine if their behaviour is affected by the candidate drugs that target the proteins identified in the first part of the study.

Bone Cancer Research Trust is keen to promote collaboration among researchers; this project benefits from the unique combination of skills and extensive experience of two laboratories who have complementary expertise in protein analysis (Dr Huang’s lab at ICR) and preclinical modelling (Professor Bovée’s lab at LUMC) respectively.

How could this project improve treatment options for chondrosarcoma patients?

This project will provide tools for doctors to predict which patients are most likely to receive long-term benefit from drugs in clinical trials, while sparing those with inadequate benefit from toxicities associated with futile drug exposure.

If successful, this work will lead to the development of new tailored treatment strategies for chondrosarcoma patients.

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