Theranostics 2020; 10(4):1960-1980. doi:10.7150/thno.39995 This issue

Review

Towards extracellular matrix normalization for improved treatment of solid tumors

Hoda Soleymani Abyaneh1,2, Maximilian Regenold2, Trevor D. McKee3, Christine Allen2✉, Marc A. Gauthier1✉

1. Institut National de la Recherche Scientifique (INRS), EMT Research Center, 1650 boul. Lionel-Boulet, Varennes, J3X 1S2, Canada.
2. Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada.
3. STTARR Innovation Centre, University Health Network, 101 College Street Room 7-504, Toronto, Ontario M5G 1L7, Canada

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Citation:
Abyaneh HS, Regenold M, McKee TD, Allen C, Gauthier MA. Towards extracellular matrix normalization for improved treatment of solid tumors. Theranostics 2020; 10(4):1960-1980. doi:10.7150/thno.39995. Available from https://www.thno.org/v10p1960.htm

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Abstract

Graphic abstract

It is currently challenging to eradicate cancer. In the case of solid tumors, the dense and aberrant extracellular matrix (ECM) is a major contributor to the heterogeneous distribution of small molecule drugs and nano-formulations, which makes certain areas of the tumor difficult to treat. As such, much research is devoted to characterizing this matrix and devising strategies to modify its properties as a means to facilitate the improved penetration of drugs and their nano-formulations. This contribution presents the current state of knowledge on the composition of normal ECM and changes to ECM that occur during the pathological progression of cancer. It also includes discussion of strategies designed to modify the composition/properties of the ECM as a means to enhance the penetration and transport of drugs and nano-formulations within solid tumors. Moreover, a discussion of approaches to image the ECM, as well as ways to monitor changes in the ECM as a function of time are presented, as these are important for the implementation of ECM-modifying strategies within therapeutic interventions. Overall, considering the complexity of the ECM, its variability within different tissues, and the multiple pathways by which homeostasis is maintained (both in normal and malignant tissues), the available literature - while promising - suggests that improved monitoring of ECM remodeling in vivo is needed to harness the described strategies to their full potential, and match them with an appropriate chemotherapy regimen.

Keywords: tumor extracellular matrix, collagen, hyaluronic acid, fibrosis, nano-formulations