Tmod-08. pdx modeling of recurrent glioblastoma for testing salvage therapies

In this study we have used a previously untreated patient derived xenograft (PDX), established from a GBM, for engrafting intracranial tumors in athymic mice that began receiving RT (2 Gy/day x 5) + TMZ (10 mg/kg x 5) on day 6 post-tumor cell implantation. Control untreated mice succumbed to growing tumor between days 22 and 26 post-tumor cell implantation. Sequential tumor bioluminescence readings revealed tumor regression in mice receiving RT + TMZ therapy. However, RT + TMZ treated tumors recurred between days 37 and 56 post-implantation. At time of tumor recurrence, mice either received no further treatment, or were given 30 mg/kg CCNU 1x/week. Thus far, 6 of 7 mice receiving no further treatment have succumbed to recurrent tumor (days 55-69 post-implantation), whereas all mice receiving CCNU treatment (n=9) remain alive at day 69 post-implantation (p < 0.001). Results from flow cytometry and immunohistochemical analysis of untreated, RT + TMZ treated, and RT + TMZ + CCNU treated tumors will be presented at the meeting. Current results indicate that we have developed an approach for in vivo modeling recurrent GBM. We anticipate that this method will prove generalizable for different GBM cell sources, and that PDX models of recurrent GBM will be useful in identifying effective salvage therapies.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MODELS Source Type: research