Tumor reversion: a dream or a reality

Abstract

Reversion of tumor to a normal differentiated cell once considered a dream is now at the brink of becoming a reality. Different layers of molecules/events such as microRNAs, transcription factors, alternative RNA splicing, post-transcriptional, post-translational modifications, availability of proteomics, genomics editing tools, and chemical biology approaches gave hope to manipulation of cancer cells reversion to a normal cell phenotype as evidences are subtle but definitive. Regardless of the advancement, there is a long way to go, as customized techniques are required to be fine-tuned with precision to attain more insights into tumor reversion. Tumor regression models using available genome-editing methods, followed by in vitro and in vivo proteomics profiling techniques show early evidence. This review summarizes tumor reversion developments, present issues, and unaddressed challenges that remained in the uncharted territory to modulate cellular machinery for tumor reversion towards therapeutic purposes successfully. Ongoing research reaffirms the potential promises of understanding the mechanism of tumor reversion and required refinement that is warranted in vitro and in vivo models of tumor reversion, and the potential translation of these into cancer therapy. Furthermore, therapeutic compounds were reported to induce phenotypic changes in cancer cells into normal cells, which will contribute in understanding the mechanism of tumor reversion. Altogether, the efforts collectively suggest that tumor reversion will likely reveal a new wave of therapeutic discoveries that will significantly impact clinical practice in cancer therapy.

Keywords: PTMs; Phenotype reversion; Revertant; SIAH1; TCTP1; Tumor reversion.

Fig. 1

Different molecular alterations involved in tumor reversion. Molecular mechanism of tumor reversion involving different alternations including PTMs such as phosphorylation, glycosylation, and other molecular changes such as microRNAs, transcription factors, RNA splicing events, the impact of the tumor microenvironment, tumor-associated macrophages, and epigenetic modifications. The arrow with an upward direction (↑) denotes an increase in the expression, and the arrow with a downward direction (↓) denotes a decrease in the expression. In the figure, gene symbols in italic means denoting gene/mRNA, and non-italic means denoting protein

Fig. 2

Protein Architecture of different proteins involved in the tumor reversion. Using the human protein reference database, the architecture of proteins involved in tumor reversion or phenotypic tumor reversion has been shown include TPT1, SIAH1, TSAP6, SETDB1, YBX1, HOXD10, PSEN1, KREV-1, ITGB1, and STAT3

Fig. 3

The mRNA expression of TPT1 across different normal human tissues. An mRNA expression of the TPT1 gene has been shown across all possible normal human tissue samples including (from left-➔ to right) appendix, bone marrow, brain, colon, duodenum, endometrium, esophagus, gall bladder, heart, kidney, liver, lung, lymph node (LN), ovary, pancreas, placenta, prostate, salivary gland, skin, small intestine, spleen, stomach, testis, thyroid, and urinary bladder. The value of the expression is shown in form of Reads Per Kilobase of transcript per million mapped reads (RPKM), which are the normalized unit for denoting transcript expression

Fig. 4

The chemical structures of compounds used for induce tumor reversion. A number of compounds have been used for reverting the phenotype of a tumor into normal. The structure of the following compounds have been drawn here using ChemDraw: Ellipticine, E7107, LY294002, Metformin, PD0325901, PD98059, Sertraline, Thiazolidinedione, Thioridazine, GGTI-2417, and GM6001