Abstract 4362: Identification and isolation of host factors in response to therapy: an approach to identify new targets for cancer therapy

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Chemotherapy remains one of the most common treatment modalities for cancer, and while initial tumor regression is usually observed, tumor re-growth and metastatic spread sometimes occur. Several preclinical studies have shown that, under certain circumstances, chemotherapy may induce angiogenesis and metastases. Several mechanisms were suggested for explaining tumor recurrence following therapy, and they are mostly related to the acquired resistance of tumor cells to a specific therapy. A recent body of evidence suggests that host derived molecular and cellular mechanisms may also account for the pro-tumorigenic and pro-metastatic effects of tumor cells following chemotherapy, yet there is still ample necessity for further investigation and isolation of such host factors. In order to solely study the host-driven pro-tumorigenic effects of chemotherapy on tumor cells, we used non-tumor bearing mice which were treated with paclitaxel chemotherapy. Subsequently, when the cytotoxic drug was cleared from the circulation, plasma was collected and used in various screening technologies in order to isolate and identify possible factors which may alter the tumor microenvironment for the tumor's advantage. We found that factors promoting bone marrow derived cell mobilization and angiogenesis, e.g., stromal-derived factor 1-α (SDF-1α) and granulocyte colony-stimulating factor (G-CSF) are substantially upregulated in the plasma of paclitaxel treated mice. In addition, increased activity of metalloproteinase 2 (MMP2) and MMP9 were also observed in plasma and bone marrow derived cells collected from mice primed with paclitaxel chemotherapy. The inductions of such host factors contributed to tumor re-growth due, in part, to their role in angiogenesis mediated by bone marrow derived cells, and to their impact on tumor cell migration and invasion activity which can lead to metastases. The pharmacologic or genetic blockade of each of these factors in conjunction with paclitaxel chemotherapy increased the treatment outcome. Additional factors are currently being evaluated and validated with respect to their impact on tumor re-growth following therapy, and will be presented in the upcoming meeting. Collectively, the evaluation of upregulated host factors in response to chemotherapy may raise potential new targets for cancer therapy, and may therefore contribute to the development of new treatment approaches for prolonging the efficacy of conventional cancer therapies. 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 4362. doi:1538-7445.AM2012-4362