Cancer prevention and therapy through the modulation of the tumor microenvironment

Stephanie C. Casey, Amedeo Amedei, Katia Aquilano, Asfar S. Azmi, Fabian Benencia, Dipita Bhakta, Alan E. Bilsland, Chandra S. Boosani, Sophie Chen, Maria Rosa Ciriolo, Sarah Crawford, Hiromasa Fujii, Alexandros G. Georgakilas, Gunjan Guha, Dorota Halicka, William G. Helferich, Petr Heneberg, Kanya Honoki, W. Nicol Keith, Sid P. KerkarSulma I. Mohammed, Elena Niccolai, Somaira Nowsheen, H. P. Vasantha Rupasinghe, Abbas Samadi, Neetu Singh, Wamidh H. Talib, Vasundara Venkateswaran, Richard L. Whelan, Xujuan Yang, Dean W. Felsher

Research output: Contribution to journalReview articlepeer-review


Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer.

Original languageEnglish (US)
Pages (from-to)S199-S223
JournalSeminars in Cancer Biology
StatePublished - Dec 1 2015


  • Cancer biology
  • Cancer prevention
  • Cancer therapy
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research


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