Investigation of CYP2W1 as a therapeutic target in childhood rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is rare but is the most common type of soft tissue cancer which is known as a ‘sarcoma’ to occur in childhood, there are around 70 new cases of this every year in the UK. RMS can arise almost anywhere in the body and is currently treated with chemotherapy drugs which can cause severe side effects.
Treatment options include cyclophosphamide and ifosamide, these are drugs that are activated once inside the body and are known as ‘prodrugs’. These damage the DNA of cancer cells and kills them however the activation is not selective inside the tumor – this happens non-selectively in the liver by enzymes known as cytochromes P450 (CYP) which cause toxicity.
To overcome this problem, new prodrugs of powerful DNA-damaging agents termed duocarmycins have been developed, these eradicate tumors expressing a new type of CYP enzyme called CYP2W1 (which is not expressed in normal tissue). The new type of prodrug is only activated directly in cancer cells where they are needed, thus preventing harmful side-effects to the rest of the body.
Ultimately, it is believed that a duocarmycin prodrug could be trialed in patients alongside other treatments to further prevent tumor growth or spread in the body. This process is called ‘metastasis’ in patients with advanced disease.