Investigating mechanisms of therapeutic resistance in DIPG
Radiation therapy is the standard treatment for DIPG. Radiation works by damaging cell's DNA. However radiation is associated with some negative side effects and some cancer cells are resistant and are able to repair damage to their DNA caused by radiation. They repair the damage using different proteins. In a publication in the Journal of Clinical Oncology, we found copy number gains and expression increases of PARP1 in DIPG. This protein could help the cancer cell repair its radiation-damaged DNA.
Small molecule inhibitors targeting DNA repair genes and proteins (like PARP1) can prevent cancer cells, but not normal cells, from fixing their radiation damaged DNA. By sensitizing cancer cells to radiation damage using these inhibitors, doctors can reduce the dose of radiation to achieve the same or greater anti-tumour effect and at the same time reducing the effect on normal cells.