Targeting the tumour stroma to improve cancer therapy

Abstract

Cancers are not composed merely of cancer cells alone; instead, they are complex ‘ecosystems’ comprising many different cell types and noncellular factors. The tumour stroma is a critical component of the tumour microenvironment, where it has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote the resistance of cancer cells to such therapies, eventually resulting in fatal disease. Therefore, novel treatment strategies should combine anticancer and antistromal agents. Herein, we provide an overview of the advances in understanding the complex cancer cell–tumour stroma interactions and discuss how this knowledge can result in more effective therapeutic strategies, which might ultimately improve patient outcomes.

Key points

  • Tumours comprise cancer cells as well as a stromal compartment with cellular and noncellular components.

  • The tumour stroma has critical roles in cancer development, progression, and metastasis.

  • Typically, anticancer therapies predominantly target cancer cells, and their effect on the tumour stroma is not taken into account.

  • The tumour stroma responds to anticancer therapies by inducing therapeutic resistance, which can ultimately lead to fatal disease.

  • Anticancer therapies should target both cancer cells and the stromal compartment to be effective and result in improved patient outcomes.

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Fig. 1: Comparison of nonmalignant stroma and tumour stroma.
Fig. 2: Tumour-stroma-mediated chemoresistance.
Fig. 3: Targeting tumour stromal cells in addition to cancer cells.

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Acknowledgements

The work of K.C.P., K.C.V., and A.E.d.G. is supported by National Cancer Institute (NCI) grants U54CA143803, CA163124, CA093900, and CA143055, as well as by the Prostate Cancer Foundation and the Patrick C. Walsh Fund. The work of K.C.V. is supported by NCI grant F32CA206394. The authors are grateful to S. Amend for editing the manuscript.

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K.C.V. and A.E.d.G. wrote the manuscript and prepared the display items. K.C.P. contributed to discussions about the contents of the manuscript. All authors reviewed and edited the manuscript before submission.

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Correspondence to Kenneth C. Valkenburg.

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Valkenburg, K.C., de Groot, A.E. & Pienta, K.J. Targeting the tumour stroma to improve cancer therapy. Nat Rev Clin Oncol 15, 366–381 (2018). https://doi.org/10.1038/s41571-018-0007-1

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