Role of Smac in Lung Carcinogenesis and Therapy
[Technical Report, Annual Report]
Thomas Jefferson University
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Ongoing efforts are focused upon generation of KRas mut Smac-- mouse model of lung cancer since there was a delay in obtaining the smac knockout mice. We were able to demonstrate the feasibility of delivering SBRT to the KRas mutant mouse model of lung cancer as described in the following publication Du S, Lockamy V, Zhou L, Xue C, LeBlanc J, Glenn S, Shukla G, Yu Y, Dicker AP, Leeper DB, Lu Y, Lu B. Stereotactic Body Radiotherapy Delivery in a GeneticallyEngineered Mouse Model of Lung Cancer. Int J Radiat Oncol Biol Phys, 2016 Nov 1963529-37. We have continued our studies using subcutaneous mouse model of lung cancer by demonstrating that CD8 T lymphocytes and TNFa are necessary to mediate the therapeutic synergism between ablative radiotherapy and a smac mimetic. Since anti-PD1 immunotherapy is shown to be superior to platin-based cytotoxic chemotherapy and change the landscape of lung cancer treatment, we have determined and demonstrated potential synergism from the combination of anti-PD1 therapy and a smac mimetic. These results will be validated in the genetically engineered mouse models once they are available.
- Medicine and Medical Research