Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment. Issue 1 (28th September 2016)

• Record Type: Journal Article
• Authors: Ivey, Jill W.; Bonakdar, Mohammad; Kanitkar, Akanksha; Davalos, Rafael V.; Verbridge, Scott S.
• Is Part Of: Cancer letters. Volume 380:Issue 1(2016)
• Page Start: 330
• Page End: 339
• Publication Date: 2016-09-28
• Subjects: Physical tumor microenvironment -- Chemcical tumor microenvironment -- Electroporation therapy -- Tumor microenvironment targeting; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.12.019
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Key physical and chemical hallmarks of the tumor microenvironment (TME) should be further leveraged as therapeutic targets. We outline the chemical (pH, oxygen) and physical (mechanical, thermal, electrical) characteristics of the TME. We review the prior work, and suggest future studies in the targeting of each of these TME hallmarks. 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.