Targeting microenvironment in cancer therapeutics.
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.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Matthew
M
Martin
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Han
H
Wei
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Tao
T
Lu
D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D059016:Tumor Microenvironment
cancer; cytokine; microenvironment; transcription factor