Cancer plasticity: Investigating the causes for this agility. (January 2023)

• Record Type: Journal Article
• Authors: Saha, Shubhraneel; Pradhan, Nikita; B, Neha; Mahadevappa, Ravikiran; Minocha, Shilpi; Kumar, Saran
• Is Part Of: Seminars in cancer biology. Volume 88(2023)
• Page Start: 138
• Page End: 156
• Publication Date: 2023-01
• Subjects: Cancer plasticity -- Cancer heterogeneity -- Epithelial-Mesenchymal Transition -- Cancer Stem Cells -- Tumor microenvironment -- Cancer therapy -- Therapy resistance; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2022.12.005
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Cancer is not a hard-wired phenomenon but an evolutionary disease. From the onset of carcinogenesis, cancer cells continuously adapt and evolve to satiate their ever-growing proliferation demands. This results in the formation of multiple subtypes of cancer cells with different phenotypes, cellular compositions, and consequently displaying varying degrees of tumorigenic identity and function. This phenomenon is referred to as cancer plasticity, during which the cancer cells exist in a plethora of cellular states having distinct phenotypes. With the advent of modern technologies equipped with enhanced resolution and depth, for example, single-cell RNA-sequencing and advanced computational tools, unbiased cancer profiling at a single-cell resolution are leading the way in understanding cancer cell rewiring both spatially and temporally. In this review, the processes and mechanisms that give rise to cancer plasticity include both intrinsic genetic factors such as epigenetic changes, differential expression due to changes in DNA, RNA, or protein content within the cancer cell, as well as extrinsic environmental factors such as tissue perfusion, extracellular milieu are detailed and their influence on key cancer plasticity hallmarks such as epithelial-mesenchymal transition (EMT) and cancer cell stemness (CSCs) are discussed. Due to therapy evasion and drug resistance, tumor heterogeneity caused by cancer plasticity has major therapeutic ramifications. Hence, it is crucial to comprehend all the cellular and molecular mechanisms that control cellular plasticity. How this process evades therapy, and the therapeutic avenue of targeting cancer plasticity must be diligently investigated. Graphical Abstract: Factors governing cancer cell plasticity can be classified into two broad categories i) cell-intrinsic factors such as DNA mutations, epigenetic changes, RNA, protein or metabolite alterations, and ii) cell extrinsic factors such as tissue perfusion, stromal influence, ECM, niche etc. ga1