Microenvironmental regulation of therapeutic response in cancer

Abstract

The tumor microenvironment (TME) not only plays a pivotal role during cancer progression and metastasis but also has profound effects on therapeutic efficacy. In the case of microenvironment-mediated resistance this can involve an intrinsic response, including the co-option of pre-existing structural elements and signaling networks, or an adaptive response of the tumor stroma following the therapeutic insult. Alternatively, in other contexts, the TME has a multifaceted ability to enhance therapeutic efficacy. This review examines recent advances in our understanding of the contribution of the TME during cancer therapy and discusses key concepts that may be amenable to therapeutic intervention.

Circulating tumor cell interactions with macrophages: implications for biology and treatment

“…Rudolf Virchow found a characteristic link between tumors and infiltrating leukocytes in 1863 and, subsequently, it became clear that tumor initiation and progression is influenced by interactions between tumor and invading normal cells (10)(11)(12). Several stromal cell types become activated and form a pro-tumorigenic microenvironment.…”

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…[149] Emerging evidences suggest that the TME play a vital role in regulating tumorigenesis, including tumor intitation, development, proliferation and metastasis, and important response to cancer therapy. [150,151] TME is sought to be one of main drivers for the accumulation of nanoparticles/ nanomedicines in the tumor and highly heterogeneous TME contribute to the differential distribution of nanomedicines within tumor. In TME, the aberrant tumor vasculatures, elevated interstitial fluid pressure (IFP) and abnormalities in ECM are major hurdles in terms of effective penetration of the nanoparticles into the tumor tissue.…”

“…In addition, hyaluronic acid (HA) has contributed to the increased IFP and hindered the diffusion and penetration of nanoparticles. [150,171,172] Therefore, modifying the components of ECM has been employed as an alternative strategy to increase the intratumoral delivery of nanomedicines ( Figure 5C). [172] By weakening or degrading the dense ECM matrix and reducing the IFP, the nanoparticle's transport in the tumor interstitium can be improved.…”

15 YEARS OF PARAGANGLIOMA: Metabolism and pheochromocytoma/paraganglioma

“…The tumor microenvironment is proving to have a pivotal role in modulating cancer progression and metastasis and has become a potential therapeutic target. The continuous interplay between cancer cells and the microenvironment generates favorable conditions that lead cancer cells to survive, grow, and spread metastases to healthy tissues (for recent reviews, see Hanahan & Weinberg (2011), Hanahan & Coussens (2012, Quail & Joyce (2013), Sounni & Noel (2013) and Klemm & Joyce (2015)). …”