EXTH-09. TDP1/TOP1 RATIO AS A PREDICTIVE INDICATOR FOR THE RESPONSE OF GLIOBLASTOMA CANCER CELLS TO IRINOTECAN TREATMENT
Other Scholarly Work
Wang, Wenjie, Silva, Monica Rodriguez, Chambers, Jeremy et al. (2017). EXTH-09. TDP1/TOP1 RATIO AS A PREDICTIVE INDICATOR FOR THE RESPONSE OF GLIOBLASTOMA CANCER CELLS TO IRINOTECAN TREATMENT
. NEURO-ONCOLOGY, 19(Suppl 6), vi74-vi75.
Wang, Wenjie, Silva, Monica Rodriguez, Chambers, Jeremy et al. (2017). EXTH-09. TDP1/TOP1 RATIO AS A PREDICTIVE INDICATOR FOR THE RESPONSE OF GLIOBLASTOMA CANCER CELLS TO IRINOTECAN TREATMENT
. NEURO-ONCOLOGY, 19(Suppl 6), vi74-vi75.
Abstract In order to make cancer chemotherapy more specific for individual patients, it would be valuable to find the predictive indicators which provide the information on cancer cell response to specific chemotherapeutic drug treatments. Topoisomerase I (TOP1) is an essential enzyme that modulates the topological structure of the chromosome during replication and transcription by cleaving and resealing the DNA. The anti-cancer drug Irinotecan (IRT) works as a topoisomerase I inhibitor, targeting topoisomerase and DNA by forming irreversible TOP1 cleavage complexes (TOP1cc), which result in an accumulation of DNA breaks. This may finally induce cell apoptosis. IRT has already been demonstrated to be effective against glioblastoma multiforme (GBM), which is the most aggressive primary brain tumor, with an extremely low median survival of around twelve months. Although TOP1 is overexpressed in most of the GBM cell lines compared with human astrocytes, TOP1 level does not correlate with IRT efficacy according to our study. Tyrosyl-DNA phosphodiesterase 1 (TDP1), a crucial repair enzyme, can rescue TOP1cc and decrease the efficacy of IRT. It has been reported that the TDP1/TOP1 ratio acts as a promising indicator for the response of small cell lung cancer to the topoisomerase I inhibitor topotecan treatment. In our study, we demonstrated that the TDP1/TOP1 activity ratio in GBM cell lines has the strongest correlation with the TOP1cc level as well as IC50 level for IRT treatment in comparison with TDP1 and TOP1 levels alone. The Pearson correlation coefficient (R) for TOP1cc level and IRT IC50 can reach 0.93 and 0.88, respectively. According to our results, the TDP1/TOP1 ratio might be a potential predictive indicator for the response of GBM cancer cells to IRT treatment and may further help to optimize the chemotherapeutic treatment protocols for individual patients.
