Abstract PL07-02: Tumor hypoxia and radiation resistance: Anything new on the horizon?

Abstract

Abstract Hypoxia is one of the key factors influencing clinical outcome after radiotherapy responsible for reduced local control that will influence overall survival, as may the hypoxic conditions by increasing malignant progression. In sharp contrast with the progresses and the rapid diffusion of functional imaging to characterize hypoxic tumors and the fact that experimental correction of tumor tumor hypoxia reverses tumor resistance to irradiation, there is no approved concomitant therapy in order to maximize response to radiotherapy for the treatment of hypoxic tumors. For decades, hypoxia was thought to act primarily on intrinsic tumor cells resistance, namely the number of clonogenic cancer stem cells surviving after radiation treatment. In the meantime, improvements into the understanding of the mechanisms triggered by hypoxia have unveiled novel molecular targets for potential combination to radiation therapy such as the interplay between STAT3 signaling and adaptation to hypoxia while the impact of tumor hypoxia on tumor microenvironment changes have expand to the immune network. Increased cellular turnover and hypoxia promote the production and release of large amounts of immunosupressive adenosine into the local microenvironment. Hypoxia can induce HIF-1a-dependent expression of arginase-1 and M2 polarization of macrophages. The spectrum of candidate therapies to target hypoxic tumors has moved from bioreductive cytotoxic agents to HIF-1, STAT3 inhibitors while growing number of immunological tools are becoming available for targeting the immune component. The ongoing EORTC 1219-ROG-HNCG/DAHANCA project 29 has gained form the past clinical attempts to target hypoxic tumors and will provide the methodology way for future clinical development of such novel combos based on optimal patients selection using biological and/or imaging criteria. Citation Format: Eric Deutsch, CYrus Chargari. Tumor hypoxia and radiation resistance: Anything new on the horizon? [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr PL07-02.