The armamentarium of therapeutics used to treat cancer patients relies heavily on ionizing radiation and chemotherapeutic drugs that severely damage DNA. The responses of tumor cells to these treatments is heavily influenced by their tumor micro environment (TME): physical contacts with structural elements comprising tissues, associations with resident and transient non-malignant cells, and interactions with numerous soluble endocrine and paracrine-acting factors all influence tumor cell behavior. Importantly, this TME is not static and dynamically responds to a variety of stimuli. This discussion will detail emerging data indicating that genotoxic cancer treatments activate highly conserved damage response programs in benign cells comprising the TME. These damage signals culminate in a developmentally conserved, powerful and diverse secretory program, the DNA Damage Secretory Program (DDSP) that generates a proangiogenic, pro-inflammatory microenvironment, and also promotes adverse tumor cell phenotypes including enhanced resistance to treatment. Key master regulators of the DDSP have been identified and offer opportunities for therapies co-targeting tumor cells along with key survival mediators from the TME. A detailed understanding of these survival signals induced in the context of genotoxic stress provides a platform to develop combinatorial strategies to improve outcomes that consider malignant cells, the tumor microenvironment, and the dynamics exerted by the treatment itself.

Citation Format: Peter S. Nelson. Targeting master regulators of damage responses in the tumor microenvironment. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr IA10. doi:10.1158/1538-7445.CHTME14-IA10

©2015 American Association for Cancer Research.
2015