Int J Biol Sci 2022; 18(7):3019-3033. doi:10.7150/ijbs.72534 This issue

Review

Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance

Aiping Zhang1,2, Kai Miao1,2,3, Heng Sun1,2,3, Chu-Xia Deng1,2,3✉

1. Cancer Center, Faculty of Health Sciences, University of Macau, Macau SAR, China.
2. Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China.
3. MOE Frontier Science Centre for Precision Oncology, University of Macau, Macau SAR, China.

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Citation:
Zhang A, Miao K, Sun H, Deng CX. Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance. Int J Biol Sci 2022; 18(7):3019-3033. doi:10.7150/ijbs.72534. Available from https://www.ijbs.com/v18p3019.htm

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Abstract

Graphic abstract

Tumor heterogeneity is one of the hallmarks of cancer and a challenge in the field of oncology. Tumor heterogeneity is the main cause of drug resistance, leading to therapeutic failure. Mechanically, tumor heterogeneity either directly affects therapeutic targets or shapes the tumor microenvironment (TME) by defining transcriptomic and phenotypic profiles to influence drug resistance. Tumor heterogeneity evolves spatially and temporally during tumor development, leading to the constant reprogramming of the TME. Advances in molecular profiling technologies and precision oncology platforms have allowed us to uncover the impact of tumor heterogeneity on drug resistance in the context of the TME. In this review, we focus on the processes during which genomic mutations drive tumor heterogeneity and the mechanisms through which tumor heterogeneity reprograms the TME to affect drug resistance and patient prognosis.

Keywords: tumor heterogeneity, tumor microenvironment, drug resistance