Targeting microenvironment in cancer therapeutics

Abstract

During development of a novel treatment for cancer patients, the tumor microenvironment and its interaction with the tumor cells must be considered. Aspects such as the extracellular matrix (ECM), the epithelial-mesenchymal transition (EMT), secreted factors, cancer-associated fibroblasts (CAFs), the host immune response, and tumor-associated microphages (TAM) are critical for cancer progression and metastasis. Additionally, signaling pathways such as the nuclear factor κB (NF-κB), transforming growth factor β (TGFβ), and tumor necrosis factor α (TNFα) can promote further cytokine release in the tumor environment, and impact tumor progression greatly. Importantly, cytokine overexpression has been linked to drug resistance in cancers and is therefore an attractive target for combinational therapies. Specific inhibitors of cytokines involved in signaling between tumor cells and the microenvironment have not been studied in depth and have great potential for use in personalized medicines. Together, the interactions between the microenvironment and tumors are critical for tumor growth and promotion and should be taken into serious consideration for future novel therapeutic approaches.

Keywords: cancer; cytokine; microenvironment; transcription factor.

Figure 1. General model of tumor and microenvironment interactions

Non cancer cells (such as CAFs, TAMs, Tregs, TILs), secreted factors (such as cytokines, chemokines, growth factors etc.), proteins (such as MMPs), transcription factors, and the ECM and EMT process are all involved in the interaction between tumor microenvironment with tumor cells. This complicated interaction can be the novel target for anti-cancer therapy in the future.