Combining Autophagy Inhibition and Temozolomide in Glioblastoma Therapy

The role of autophagy in cancer is complex, yet there is promise in the addition of autophagy inhibitors to existing therapies. For example, as the futile rounds of DNA repair induced by Temozolomide (TMZ) have been proposed to deplete the energy reserves of the tumour cells, adding chloroquine to the current treatment schedule is currently being evaluated for Glioblastoma treatment. As we have previously shown that TMZ functions in a more complex manner as originally anticipated, we investigated the potential of combining this chemotherapeutic with either Chloroquine or Bafilomycin A, two distinct (relatively unspecific) inhibitors of late stage autophagy. Both inhibitors had a potent effect on cell viability of established cell lines and differentiated patient-derived cells, but only marginally affected stem cell-like cells. The addition of TMZ did not influence these findings drastically.

Our data strongly suggest that chloroquine and Bafilomycin A or two substances of significant interest for future therapeutic options in Glioblastoma treatment and that the presence or absence of TMZ does not strongly contribute to their effectiveness. However, our data do not indicate that it is necessarily the autophagy inhibition induced by these substances that makes the cells more susceptible to cell death.