Abstract IA21: Targeting WEE1 kinase to potentiate chemoradiation in the treatment of pancreatic cancer

Pancreas cancer is projected to cause approximately 42,000 deaths in 2016, making it the third greatest cause of cancer mortality (behind lung and colorectal, but greater even than breast). Systemic failure remains the dominant cause of death, although local failure is responsible for up to 1/3 of the pancreatic cancer related mortality. We have focused on improving the treatment of locally advanced pancreatic cancer, defined as disease which cannot be resected but has not overtly metastasized, where the issue of local control becomes even more important, and have hypothesized that the treatment of locally advanced pancreatic cancer will require control of both the gross primary tumor as well as the microscopic disease that exists in virtually every patient. Gemcitabine has been a mainstay of treatment for pancreatic cancer, and we have standardized combining it with radiation for locally advanced disease. Because our initial studies revealed that activation of the DNA damage response, particularly activation of CHK1 and WEE1, were crucial in the defense pancreatic cancers mount against chemotherapy and radiation, we have studied the effect of CHK1 and WEE1 inhibitors on gemcitabine and gemcitabine-radiation mediated cytotoxicity. These inhibitors abrogate the G2 checkpoint after DNA damage. The initial hypothesis for using CHK1 and WEE1 inhibitors was that cancer cells lacking a p53 checkpoint would be selectively sensitized, compared to normal cells, because normal cells wo...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Therapies Targeting Checkpoints and Mismatch Repair: Oral Presentations - Invited Abstracts Source Type: research