Abstract 745: Development of gamma-H2AX assay to assess toxicity and efficacy from chemotherapy in circulating tumor cells (CTCs) and peripheral blood lymphocytes

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL CTC methodology has been recently adopted following FDA approval of the Veridex CellSearch for the detection of CTCs and offers prognostic value in various solid tumors including breast, colorectal, and prostate cancer. gamma-H2AX is an established marker for double strand breaks from DNA damage, and this is particularly evident and has been seen after exposure to ionizing radiation and exposure to topoisomerase inhibitors. Moreover prolonged gamma-H2AX expression has been observed in repair deficiencies after DNA damage where there may be delays in DNA repair and persistence of H2AX. H2AX may therefore serve as an excellent marker not only of toxicity but the efficacy of the chemotherapy. We have been using human tumor cell lines to expose them to chemotherapeutic agents in the laboratory to detect gamma-H2AX levels and the dynamic changes thereof following exposure to cytotoxic chemotherapy. Our results reveal clear time-dependent upregulation of gamma-H2AX in treated cells. This is being adopted for use on CTCs as well as blood lymphocytes with a goal of making correlations with toxicity to chemotherapy in treated patients as well as use of this assay to mark the efficacy of chemotherapy in CTCs. We are applying quantum dot technology to detection of gamma-H2AX in cells recovered from blood and this is being incorporated into a clinical protocol. This assay has potential to impact on monitoring of chemotherapy with regard to both toxicity and efficacy in the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 745. doi:1538-7445.AM2012-745