Treatment resistance and tumor recurrence
Following, or even during radiation-chemotherapy glioblastomas will recur. In >90 of cases locally and directly adjacent to the primary site of the tumor. Recurrent glioblastomas are not responsive to any of the known treatments today. The reason may be resistance mechanisms that evolve in response to the initial radiation-chemotherapy.
Resistant glioblastoma cell clones surviving radiation-chemotherapy show altered global transcription profiles. Within the bulk of the recurrent tumor glioblastoma cell populations with distinct transcription profiles and resistance mechanism expand and repopulate the tumor. On a molecular level the recurrent tumor thus is profoundly different from the primary tumor and its transcription profiles prior to any treatment.
Therefore, the search for effective treatments for recurrent glioblastomas can no longer be based on first line strategies. In fact, after intense efforts today no cytotoxic or tumor modulating agent active in primary glioblastomas has been found active in recurrent tumors. This calls for rethinking of these profoundly unsuccessful strategies in development of new treatments for recurrent glioblastoma.