Combined inhibition of Wee1 and PARP1/2 for radiosensitization in pancreatic cancer.

ABSTRACT:

Purpose

While the addition of radiation to chemotherapy improves survival in patients with locally advanced pancreatic cancer, more effective therapies are urgently needed. Thus, we investigated the radiosensitizing efficacy of the novel drug combination of Wee1 and PARP1/2 inhibitors (AZD1775 and olaparib, respectively) in pancreatic cancer.

Experimental design

Radiosensitization of AsPC-1 or MiaPaCa-2 human pancreatic cancer cells was assessed by clonogenic survival and tumor growth assays. Mechanistically, the effects of AZD1775, olaparib, and radiation on cell cycle, DNA damage (γH2AX), and homologous recombination repair (HRR) were determined.

Results

Treatment of AsPC-1 and MiaPaCa-2 cells with either AZD1775 or olaparib caused modest radiosensitization, whereas

SUBMITTER: Karnak D 

PROVIDER: S-EPMC4184968 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature