Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

Abstract

Cancer is a disease which frequently has a poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments frequently impedes the clinical outcomes. Besides the active resistance driven by genetic and epigenetic alterations in tumor cells, the tumor microenvironment (TME) has also been reported to be a crucial regulator in tumorigenesis, progression, and resistance. Here, we propose that the adaptive mechanisms of tumor resistance are closely connected with the TME rather than depending on non-cell-autonomous changes in response to clinical treatment. Although the comprehensive understanding of adaptive mechanisms driven by the TME need further investigation to fully elucidate the mechanisms of tumor therapeutic resistance, many clinical treatments targeting the TME have been successful. In this review, we report on recent advances concerning the molecular events and important factors involved in the TME, particularly focusing on the contributions of the TME to adaptive resistance, and provide insights into potential therapeutic methods or translational medicine targeting the TME to overcome resistance to therapy in clinical treatment.

A Novel Risk Model Based on Lipid Metabolism-Associated Genes Predicts Prognosis and Indicates Immune Microenvironment in Breast Cancer

“…The tumor microenvironment (TM) is a crucial regulator of malignancy ( Wu et al, 2021 ). In particular, the tumor immune microenvironment, which reflects the immune status of the tumor tissues, performs critical functions, and has attracted increasing attention ( Pitt et al, 2016 ; Locy et al, 2018 ; Lei et al, 2020 ).…”

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

“…Studies of immune infiltration have shown that the tumor immune microenvironment has a key role in cancer progression and affects the clinical outcomes of cancer patients (Murciano-Goroff et al, 2020;Zhang and Zhang, 2020). As immune cells are the cellular basis of immunotherapy, an in-depth understanding of immune infiltration in the tumor immune microenvironment can reveal underlying molecular mechanisms and provide new strategies to improve the efficacy of immunotherapy (Wu et al, 2021). A key result of the present work was that PER1 expression was closely related to the infiltration levels of a variety of immune cells.…”

Proteomics, Personalized Medicine and Cancer

“…A key control on the development of malignant tumors, which typically have poor prognosis, is the activation of invasion and metastasis, which acts in conjunction with three other hallmarks (sustained angiogenesis, evading immune response and tumor-promoting inflammation). It is now realized that the acquisition of these hallmarks is further controlled by contributions from the tumor microenvironment, consisting of the extracellular matrix [ 90 ], stromal cells and immune cells, but the precise dynamics between the nontumor microenvironment (NTME), tumor microenvironment (TME) [ 105 ] and the systemic immune system remains abstruse. A high-dimensional proteomic and transcriptomic approach was used to examine this in HCC.…”