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Novel RNAi Therapeutic Enhancement of Temozolomide to Treat Cancer

详细技术说明

None

*Abstract

BackgroundMelanoma and glioblastoma are important causes of death due to malignancy in the United States. The incidence of cutaneous melanoma has doubled in the past 10 years and is increasing more rapidly than all other solid tumors. Although early detection of a primary melanoma provides an >85% cure rate, stage IV disease has a very poor prognosis with a median survival of 6-8 months.

Temozolomide (TMZ) has emerged as a novel treatment for glioblastoma, melanoma and other solid tumors. As with many chemotherapeutic agents, the effectiveness of TMZ depends on the induction of genomic DNA damage. This damage is often repaired by the body causing drug resistance. A need remains for enhancing the efficacy of anticancer agents such as TMZ and other alkylating agents.

TechnologyInvestigators at the University of Pittsburgh have found that TMZ induces damage that is repaired by ß-pol and the BER pathway. ß-pol deficiency renders cells highly sensitive to TMZ due to failure to repair the 5’dRP lesion. This finding suggests that inhibition of ß-pol will render tumor cells highly sensitive to TMZ chemotherapy.

The investigators have utilized RNA-interference to inhibit the expression or activity of the enzyme ß-pol in cells making normally resistant cells highly sensitive to TMZ.

Application

* Targeted treatment for various cancers such as breast, anaplastic astrocytoma, glioblastoma, metastatic melanoma, leukemia, lymphoma, aerodigestive tract, pancreatic, neuroendocrine tumors and brain metastasis.

Advantages* Novel RNAi approach to sensitizing tumors to TMZ treatment

Stage of Development1) Preclinical animal data is available.2) The University would welcome opportunities for sponsored-research collaborations to further support this research endeavor.

*Principal Investigation

Name: Robert Sobol

Department: Med-Pharmacology and Chemical Biology

国家/地区

美国