Cancer treatment with radiation-chemotherapy rapidly induces molecular pathways for both resistance and new therapeutic targets

FaDu tumors were implanted into Athymic mice then treated with HSP90 inhibitor Onalespib (5 days per week, 55mg/kg for 2 weeks), radiation (3 x 2 Gy for 1 week) or combination (2 week Onalespib, 1 week radiation concurrent) The purpose of this study was to understand short term (1 week and 2 week post treatment) gene changes in FaDu tumors that had been injected into hind limbs of athymic mice. A drug treatment, a radiation treatment, a combination treatment, or sham treatment was used. Mice with untreated tumors required early euthanasia as tumors became too large. Treated tumors were collected 5 and 12 days post treatment start while UNtreated tumors were collected Day 5 and Day 8. Control Day 1 samples (mice euthanized on the start date of treatment) were compared to other groups. Radiation, Onalespib or combination treatment induced gene changes to FaDu human xenograft samples grown on athymic mice were collected after 1 or 2 weeks of treatment. Tumor samples were collected and used for RNA microarray. 37 samples collected total, 3 samples minimum per treatment, Control Day 1, Control Week 1, Control Week 2, Drug Week 1 (55mg/kg 5 days per week), Drug Week 2, XRT (radiation, 3 x 2Gy, every other day) Week 1, XRT Week 2 (radiation week 1, no radiation week 2), Drug+XRT Week 1 (1 week radiation, 1 week drug on same schedule as Drug alone and XRT alone), Drug+XRT Week 2 (2 weeks of Drug, 1 week XRT)