Advances in Tumor-Stroma Interactions: Emerging Role of Cytokine Network in Colorectal and Pancreatic Cancer

Abstract

Cytokines are a family of soluble factors (Growth Factors (GFs), chemokines, angiogenic factors, and interferons), which regulate a wide range of mechanisms in both physiological and pathological conditions, such as tumor cell growth and progression, angiogenesis, and metastasis. In recent years, the growing interest in developing new cancer targeted therapies has been accompanied by the effort to characterize Tumor Microenvironment (TME) and Tumor-Stroma Interactions (TSI). The connection between tumor and stroma is now well established and, in the last decade, evidence from genetic, pharmacological, and epidemiological data supported the importance of microenvironment in tumor progression. However, several of the mechanisms behind TSI and their implication in tumor progression remain still unclear and it is crucial to establish their potential in determining pharmacological response. Many studies have demonstrated that cytokines network can profoundly affect TME, thus displaying potential therapeutic efficacy in both preclinical and clinical models. The goal of this review is to give an overview of the most relevant cytokines involved in colorectal and pancreatic cancer progression and their implication in drug response.

Figure 1

Schematic illustration of the cytokines role in tumorigenesis. Cytokines are released by both tumor and stromal cells, including immune cells like macrophages, B and T lymphocytes, dendritic cells, and endothelial cells and fibroblasts. The binding of cytokines to their receptors on surface of targeted cells causes the activation of intracellular signaling cascades with protumoral and/or antitumoral properties.