Tumors are composed of both cancer cells and host cells including stromal cells (e.g., fibroblasts and mesenchymal cells), vascular endothelial cells, and immune/inflammatory cells (e.g., macrophages, monocytes, neutrophils and lymphocytes). The growth, invasiveness and metastatic potential of cancer cells are influenced by various neighboring cells that comprise the so-called tumor microenvironment. Therefore, the precise understanding of interaction and communication between cancer cells and surrounding environment is very essential for the discovery of novel anticancer targets and development of efficient therapeutic and preventive strategies.

The concept that the microenvironment of developing tumor is a crucial regulator of carcinogenesis was originally proposed by Paget in his famous ‘seed-and-soil’ hypothesis. During carcinogenesis, there might be molecular lesions in cells of the microenvironment and in epithelial cells themselves. It is hence necessary to consider the microenvironment of cancer and its associated epithelium as a whole. Recently much attention has focused on tumor microenvironment as an integral and essential part of developing innovative new cancer therapeutic and preventive regimes. The success of chemo-/radiotherapy as well as chemoprevention depends more fundamentally on their comprehensive modulation of the tumor microenvironment.

There is mounting evidence from preclinical and clinical studies that persistent inflammation functions as a driving force in the journey to cancer. While inflammation stimulates development of cancer, components of the tumor microenvironment, such as tumor cells, stromal cells in surrounding tissue and infiltrated inflammatory/immune cells generate an intratumoral inflammatory state by aberrant expression or activation of some proinflammatory molecules. Some proinflammatory mediators can turn on the angiogenic switches mainly controlled by vascular endothelial growth factor, thereby inducing inflammatory angiogenesis and tumor cell-stroma communication. This will accelerates tumor angiogenesis, metastasis and invasion. In this context, the use of anti-inflammatory and proresolving agents to control the function and behavior of cells in the inflammatory microenvironment will be an important approach to the overall control of cancer. Supported by the Global Core Research Center grant from the National Research Foundation, Republic of Korea.

References:

1. Crawford S. (2013) Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer, chemotherapy. Front Pharmacol. 4: 68.

2. Fang H, Declerck YA (2013) Targeting the tumor microenvironment: from understanding pathways to effective clinical trials. Cancer Res. 73: 4965-4977.

3. Oshima H, Oshima M (2012) The inflammatory network in the gastrointestinal tumor microenvironment: lessons from mouse models..J Gastroenterol. 47(2):97-106.

4. Albini A, Sporn MB (2007) Tumor microenvironment as a target for chemoprevention. Nat. Rev. Cancer, 7: 139-147.

5. Hanna E, Quick J, Libutti SK (2009) The tumour microenvironment: a novel target for cancer therapy. Oral Dis. 15: 8-17

6. Erickson AC, Barcellos-Hoff MH (2003) The not-so innocent bystander: the microenvironment as a therapeutic target in cancer. Expert Opin Ther Targets.7:71-88

7. Kundu JK, Surh YJ (2008) Inflammation: Gearing the journey to cancer. Mutat Res. 659:15-30.

Citation Format: Young-Joon Surh. Targeting inflammatory microenvironment for cancer chemoprevention and therapy. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED01-01.

©2013 American Association for Cancer Research.
2013