Praveen Krishna Veerasubramanian1,2, Annie Trinh2,3, Navied Akhtar1,2, Wendy F Liu1,2,4, Timothy L Downing1,2,3,5. 1. Department of Biomedical Engineering, University of California-Irvine, Irvine, CA, USA. 2. The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine, Irvine, CA, USA. 3. Department of Microbiology and Molecular Genetics, University of California-Irvine, Irvine, CA, USA. 4. Department of Chemical and Biomolecular Engineering, University of California-Irvine, Irvine, CA, USA. 5. NSF-Simons Center for Multiscale Cell Fate Research, University of California-Irvine, Irvine, CA, USA.
Abstract
PURPOSE OF REVIEW: The tumor microenvironment (TME) is an amalgam of multiple dysregulated biophysical cues that can alter cellular behavior through mechanotransductive signaling and epigenetic modifications. Through this review, we seek to characterize the extent of biophysical and epigenetic regulation of cancer stemness and tumor-associated immune cells in order to identify ideal targets for cancer therapy. RECENT FINDINGS: Recent studies have identified cancer stemness and immune action as significant contributors to neoplastic disease, due to their susceptibility to microenvironmental influences. Matrix stiffening, altered vasculature, and resultant hypoxia within the TME can influence cancer stem cell (CSC) and immune cell behavior, as well as alter the epigenetic landscapes involved in cancer development. SUMMARY: This review highlights the importance of aberrant biophysical cues in driving cancer progression through altered behavior of CSCs and immune cells, which in turn sustains further biophysical dysregulation. We examine current and potential therapeutic approaches that break this self-sustaining cycle of disease progression by targeting the presented biophysical and epigenetic signatures of cancer. We also summarize strategies including the normalization of the TME, targeted drug delivery, and inhibition of cancer-enabling epigenetic players.
PURPOSE OF REVIEW: The tumor microenvironment (TME) is an amalgam of multiple dysregulated biophysical cues that can alter cellular behavior through mechanotransductive signaling and epigenetic modifications. Through this review, we seek to characterize the extent of biophysical and epigenetic regulation of cancer stemness and tumor-associated immune cells in order to identify ideal targets for cancer therapy. RECENT FINDINGS: Recent studies have identified cancer stemness and immune action as significant contributors to neoplastic disease, due to their susceptibility to microenvironmental influences. Matrix stiffening, altered vasculature, and resultant hypoxia within the TME can influence cancer stem cell (CSC) and immune cell behavior, as well as alter the epigenetic landscapes involved in cancer development. SUMMARY: This review highlights the importance of aberrant biophysical cues in driving cancer progression through altered behavior of CSCs and immune cells, which in turn sustains further biophysical dysregulation. We examine current and potential therapeutic approaches that break this self-sustaining cycle of disease progression by targeting the presented biophysical and epigenetic signatures of cancer. We also summarize strategies including the normalization of the TME, targeted drug delivery, and inhibition of cancer-enabling epigenetic players.
Entities:
Keywords:
biomechanics; cancer stemness; cancer therapeutics; epigenetics; immunoevasion; mechanotransduction; tumor heterogeneity
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