Evolvability and emergence of tumor heterogeneity as a space–time function. (January 2023)

• Record Type: Journal Article
• Authors: Saha, Bhaskar; Vannucci, Luca; Saha, Baibaswata; Tenti, Paolo; Baral, Rathindranath
• Is Part Of: Cytokine. Volume 161(2023)
• Publication Date: 2023-01
• Subjects: Human endogenous retroviruses -- Evolvability of tumor -- Tumor heterogeneity -- Metabolic heterogeneity -- Tumor metastasis heterogeneity; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2022.156061
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: Endogenous retroviruses are a major cause of the intra- and inter-tumor heterogeneity. Tumor cells de-differentiate to acquire cancer stem cell properties and metastasize. Multiple factors that contribute to tumor heterogeneity exhibit space–time function. Tumor heterogeneity throws up huge challenges to successful anti-cancer therapy. Abstract: The loss of control of cell proliferation, apoptosis regulation and contact inhibition leads to tumor development. While benign tumors are restricted to their primary space, i.e. where these tumors first originate, the metastatic tumors not only disseminate- facilitated by hypoxia-driven neovascularization- to distant secondary sites but also show substantial changes in metabolism, tissue architectures, gene expression profiles and immune phenotypes. All these alterations result in radio-, chemo- and immune-resistance rendering these metastatic tumor cells refractory to therapy. Since the beginning of the transformation, these factors- which influence each other- are incorporated to the developing and metastasizing tumor. As a result, the complexities in the heterogeneity of tumor progressively increase. This space–time function in the heterogeneity of tumors is generated by various conditions and factors at the genetic as well as microenvironmental levels, for example, endogenous retroviruses, methylation and epigenetic dysregulation that may be etiology-specific, cancer associated inflammation, remodeling of the extracellular matrix and mesenchymal cell shifted functions. On the one hand, these factors may cause de-differentiation of the tumor cells leading to cancer stem cells that contribute to radio-, chemo- and immune-resistance and recurrence of tumors. On the other hand, they may also enhance the heterogeneity under specific microenvironment-driven proliferation. In this editorial, we intend to underline the importance of heterogeneity in cancer progress, its evaluation and its use in correlation with the tumor evolution in a specific patient as a field of research for achieving precise patient-tailored treatments and amelioration of diagnostic (monitoring) tools and prognostic capacity.