Combining EZH2 inhibition and Radiotherapy for the Treatment of Childhood Rhabdomyosarcomas

Every year over 60 children and teenagers in the UK are diagnosed with rhabdoymosarcoma (RMS), yet treatment regimes and survival rates have remained largely unchanged for decades. Radiotherapy is an important component of treatment for RMS. However, disease recurring at radiotherapy sites and long-term side effects following radiation are common problems. Treatment strategies that increase sensitivity to radiotherapy at the tumour site could reduce recurrences or allow lower doses of radiation to be given. This offers great promise of increasing patient survival and reducing harmful side effects. We have previously shown that a protein called EZH2 is present at higher levels in RMS than normal tissues and that by decreasing EZH2 in tumour cells we can reduce their growth. As radiotherapy kills cells by damaging DNA and EZH2 is linked to the cells’ ability to repair damage to DNA, we will test the hypothesis that reducing EZH2 activity will enhance the response of RMS cells to radiation. In parallel, we will test a marker of response to this combination treatment. This pilot study may provide rationale for further preclinical testing. As drugs against EZH2 are currently undergoing clinical trials for other cancers, this combination could be readily introduced for RMS.

Grant Award – Kidscan Pump Priming Grant (2016)
Funding Award – £5,000
Funding Awarded To – Dr Zoe Walters
Research Location – Institute of Cancer Research (ICR)
Lead Researcher – Dr Zoe Walters