Signal Transduction Inhibition/Experimental Therapeutics
The poor response of malignant gliomas to conventional therapies, such as cytotoxic chemotherapy or radiotherapy, reflects resistance of these tumors to undergoing apoptosis in response to DNA damage or mitogen depletion. This group of researchers, in collaboration with national groups, study inhibitors of multiple cellular signaling pathways in order to design novel therapeutic combinations.
- The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has significant apoptosis-inducing activity in some glioma cell lines, although many lines are either moderately or completely resistant, which limits the therapeutic applicability of this agent. The proteasome inhibitor bortezomib markedly enhanced TRAIL-induced apoptosis of glioma cells by inhibiting the NF-kB pathway (Jane et.al., Mol Cancer Ther. 2011, 10:198-208).
- A subset of children with the generally fatal brain-stem glioma experienced long-term progression-free survival on treatment with gefitinib and radiation (Pollack et.al., Neuro Oncol. 2011, 13:290-7).
- Both carboplatin and vinblastine have demonstrated single-agent activity in children with low-grade gliomas. In a phase 1 trial evaluating 2 different schedules of these 2 agents in combination, BTP investigators in collaboration with the Children's Oncology Group, found improvement in 7 of 9 patients with visual pathway tumors and acute visual changes prior to enrollment (Jakacki et.al., Neuro Oncol. 2011, 13:910-5).
|Drappatz, Jan, MD
|Jakacki, Regina, MD
|Hamilton, Ronald, MD
|Pollack, Ian, MD