Recent Advances in Cancer Plasticity: Cellular Mechanisms, Surveillance Strategies, and Therapeutic Optimization

Abstract

The processes of recurrence and metastasis, through which cancer relapses locally or spreads to distant sites in the body, accounts for more than 90% of cancer-related deaths. At present there are very few treatment options for patients at this stage of their disease. The main obstacle to successfully treat advanced cancer is the cells' ability to change in ways that make them resistant to treatment. Understanding the cellular mechanisms that mediate this cancer cell plasticity may lead to improved patient survival. Epigenetic reprogramming, together with tumor microenvironment, drives such dynamic mechanisms favoring tumor heterogeneity, and cancer cell plasticity. In addition, the development of new approaches that can report on cancer plasticity in their native environment have profound implications for studying cancer biology and monitoring tumor progression. We herein provide an overview of recent advancements in understanding the mechanisms regulating cell plasticity and current strategies for their monitoring and therapy management.

Keywords: cancer plasticity; heterogeneity; liquid biopsy; recurrence; stem cell.

Figure 1

Mechanisms governing CSC plasticity model. Intra-tumor heterogeneity relies on the capacity to shift dynamically and reversibly between CSC and non-CSC/differentiated state. Tumor cell modifications as genetic and epigenetic alterations and microenvironment perturbations as inflammation, injury, and senescence represent the major causes of cancer cells plasticity. Moreover, CSCs exhibit an induced epithelial-to-mesenchymal transition (EMT) program and, particularly, they display an intermediate state of EMT. This process depends on both genetic mutations, epigenetic modifications and transcriptional modulation of cancer cells and signals provided by the tumor microenvironment (i.e., growth factors, cytokines, CAFs or TAMs). Created with BioRender.com.