Tripathi Avantika, Kashyap Anjali, Tripathi Greesham, Yadav Joni, Bibban Rakhi, Aggarwal Nikita, Thakur Kulbhushan, Chhokar Arun, Jadli Mohit, Sah Ashok Kumar, Verma Yeshvandra, Zayed Hatem, Husain Amjad, Bharti Alok Chandra, Kashyap Manoj Kumar
Amity Stem Cell Institute, Amity Medical School, Amity University Haryana, Panchgaon, Haryana, Manesar (Gurugram), -122413, India.
Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, Punjab, India.
Biomark Res. 2021 May 6;9(1):31. doi: 10.1186/s40364-021-00280-1.
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.
肿瘤向正常分化细胞的逆转曾被视为梦想，如今已濒临成为现实。诸如微小RNA、转录因子、可变RNA剪接、转录后及翻译后修饰、蛋白质组学的可用性、基因组编辑工具以及化学生物学方法等不同层次的分子/事件，为操纵癌细胞向正常细胞表型逆转带来了希望，尽管证据尚不明显但确凿无疑。尽管取得了进展，但仍有很长的路要走，因为需要精确微调定制技术，以更深入了解肿瘤逆转。使用现有基因组编辑方法的肿瘤消退模型，再结合体外和体内蛋白质组学分析技术，已显示出初步证据。本综述总结了肿瘤逆转的进展、当前问题以及在这一未知领域中仍未解决的挑战，这些挑战涉及成功调节细胞机制以实现肿瘤逆转的治疗目的。正在进行的研究重申了理解肿瘤逆转机制的潜在前景，以及在肿瘤逆转的体外和体内模型中进行必要优化的必要性，以及将这些成果转化为癌症治疗的可能性。此外，据报道，治疗性化合物可诱导癌细胞向正常细胞发生表型变化，这将有助于理解肿瘤逆转的机制。总体而言，这些努力共同表明，肿瘤逆转可能会带来新一轮的治疗发现，对癌症治疗的临床实践产生重大影响。
