Rhabdomyosarcoma (RMS) is a rare type of cancer but is the most prevalent sarcoma (cancer of soft tissues e.g. fat, muscle, blood vessels and nerves) to occur in childhood with approximately 70 new cases in the UK annually.
RMS can arise virtually anywhere in the body and is currently treated with chemotherapy drugs that cause severe side effects for patients (medications that essentially poison a tumour and prevent it dividing so the tumour doesn’t grow, they also damage healthy cells – hence the side effects). Treatment options include cyclophosphamide and ifosamide, drugs that are ‘activated’ once inside the body (‘prodrugs’), where they then damage the DNA (genetic information that tells cells to divide and passes on information) of cancer cells and kills them.
The problem is that this activation doesn’t occur inside the tumour – it happens non‐selectively in the liver by enzymes (proteins that speed up chemical reactions in the cells) known as cytochromes P450 (CYP), which causes toxicity as the drugs are free to move around the body damaging otherwise healthy cells. To overcome this problem, we have developed new prodrugs of powerful DNA‐damaging agents termed duocarmycins that eradicate tumours expressing a new type of CYP enzyme called CYP2W1 (this enzyme is not expressed in normal tissue so is only present around tumour sites). This means that the new type of prodrug is only activated directly in cancer cells where they are needed, preventing harmful side‐effects in the rest of the body.
Ultimately, we believe a duocarmycin prodrug could be trialled in patients alongside other treatments to further prevent tumour growth or spread in the body (the process called ‘metastasis’) in patients with advanced disease.
Grant Award – Fellowship 2019-2022
Funding Award – £63,675
Funding Awarded to – Professor Klaus Pors
Research Location – Brunel University
Lead Researcher – Professor Klaus Pors
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