title: Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment.
abstract: Tumors are highly heterogeneous at the patient, tissue, cellular, and molecular levels. This multi-scale heterogeneity poses significant challenges for effective therapies, which ideally must not only distinguish between tumorous and healthy tissue, but also fully address the wide variety of tumorous sub-clones. Commonly used therapies either leverage a biological phenotype of cancer cells (e.g. high rate of proliferation) or indiscriminately kill all the cells present in a targeted volume. Tumor microenvironment (TME) targeting represents a promising therapeutic direction, because a number of TME hallmarks are conserved across different tumor types, despite the underlying genetic heterogeneity. Historically, TME targeting has largely focused on the cells that support tumor growth (e.g. vascular endothelial cells). However, by viewing the intrinsic physical and chemical alterations in the TME as additional therapeutic opportunities rather than barriers, a new class of TME-inspired treatments has great promise to complement or replace existing therapeutic strategies. In this review we summarize the physical and chemical hallmarks of the TME, and discuss how these tumor characteristics either currently are, or may ultimately be targeted to improve cancer therapies.
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA.
authors.forename: Jill W
authors.initials: JW
authors.lastname: Ivey
authors.affiliation: Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bonakdar
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Kanitkar
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA; Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA. Electronic address: sverb@vt.edu.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Verbridge
mesh_terms: D055011:Ablation Techniques / Q000379:methods; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers
keywords: Chemcical tumor microenvironment; Electroporation therapy; Physical tumor microenvironment; Tumor microenvironment targeting