Abstract B51: Examining the differential cellular response of pancreatic cancer cell lines to 12C vs. photon irradiation

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is expected by 2020 to become the second most common cause of cancer-related deaths globally. The 5-year overall survival rate for patients with locally advanced nonresectable (LANR) PDAC is ~12%, likely because of the inherent resistance to conventional radio- and chemotherapy and the fact that the majority of pancreatic cancer patients present with advanced disease. While median overall survival (mOS) for chemoradiotherapy is 15.2 months, mOS determined from a retrospective analysis of patients with LANR PDAC treated with carbon ion therapy (CIRT) and concurrent gemcitabine was 21.5 months. Recently, UTSW initiated a randomized multi-institutional phase III trial (CIPHER) comparing CIRT to intensity-modulated radiation therapy for LANR PDAC. In conjunction with CIPHER, we initiated preclinical studies to exploit genetic vulnerabilities amenable to CIRT vs. IMRT. Eight PDAC cell lines with known genetic backgrounds were exposed to g-rays and 12C ions to determine the range of relative biologic effectiveness of 12C ion exposure. A specific area of interest is the DNA damage response given the vulnerability of tumor cells with slight deficiencies in genes associated with homologous recombination or replication fork maintenance to 12C ion exposure that is not seen with g-rays. Other endpoints being examined include differences in cell signaling that may affect inflammatory and immune responses, alterations to the microenvironment, or other signaling pathways that may identify druggable targets for combination with CIRT. Citation Format: Janapriya Saha, Michael D. Story, Anthony Davis, Brock J. Sishc. Examining the differential cellular response of pancreatic cancer cell lines to 12C vs. photon irradiation [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B51.