Cancer cell reprogramming: a promising therapy converting malignancy to benignity

Abstract

In the past decade, remarkable progress has been made in reprogramming terminally differentiated somatic cells and cancer cells into induced pluripotent cells and cancer cells with benign phenotypes. Recent studies have explored various approaches to induce reprogramming from one cell type to another, including lineage-specific transcription factors-, combinatorial small molecules-, microRNAs- and embryonic microenvironment-derived exosome-mediated reprogramming. These reprogramming approaches have been proven to be technically feasible and versatile to enable re-activation of sequestered epigenetic regions, thus driving fate decisions of differentiated cells. One of the significant utilities of cancer cell reprogramming is the therapeutic potential of retrieving normal cell functions from various malignancies. However, there are several major obstacles to overcome in cancer cell reprogramming before clinical translation, including characterization of reprogramming mechanisms, improvement of reprogramming efficiency and safety, and development of delivery methods. Recently, several insights in reprogramming mechanism have been proposed, and determining progress has been achieved to promote reprogramming efficiency and feasibility, allowing it to emerge as a promising therapy against cancer in the near future. This review aims to discuss recent applications in cancer cell reprogramming, with a focus on the clinical significance and limitations of different reprogramming approaches, while summarizing vital roles played by transcription factors, small molecules, microRNAs and exosomes during the reprogramming process.

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

“…With the high mortality rate of cervical cancers, more information is needed regarding detection and treatment of the diseased. In this regard, several investigators have begun to examine extracellular vesicles (EVs) and their role in disease protection [2], as disease biomarkers [3][4][5] and/or as a cargo/vaccine agents for cervical cancer [6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Cellular Reprogramming—A Model for Melanoma Cellular Plasticity

“…Dedifferentiation by ectopic expression of reprogramming transcription factors such as OSKM, have been reported in a variety of cancers including melanoma [27,49,50], Leukemia [51], gastrointestinal cancer [52], osteosarcoma [53], colorectal cancer [52], hepatocellular carcinoma [54], bladder cancer [55], neuroblastoma [56], pancreatic ductal adenocarcinoma [57] and others. However, the molecular mechanisms that underlie the process of dedifferentiation are still not completely understood [19,58].…”

“…Deciphering what exactly happens on a molecular level during cellular reprogramming might also help us to understand cancer initiation, progression and recurrence in a way that will enable us to improve the efficacy of treatments considerably. For this purpose, new in vitro models for studying cellular plasticity and CSCs are required [19]. In this review, we summarize the current knowledge about cellular reprogramming and the use of partial reprogramming as a model to study cellular plasticity during melanoma progression.…”

Cancer: A turbulence problem

“…Active matter systems suggest that turbulent energy cascades may help explain collective cell migration and pattern formation systems [70 , 71] . The cytoskeletal protein microtubules and actin are being recognized as candidates for these active turbulence models, wherein the swarming/flocking behaviors of proteins can phase-transition from Brownian motion to the turbulent regime of Navier-Stokes equations, at relatively low Reynolds numbers [72] .…”