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.

Association of COVID-19 with Comorbidities: An Update

“…Besides the anti-inflammatory action of metformin, it is potentially used against the SARS-CoV-2 virus. , Metformin acts through inhibiting the virus–host-cell association as well as prevents the expression of ACE2 through the activation of adenosine monophosphate-activated protein kinase. Another promising molecule, DPP-4 antagonist (Linagliptin), an anti-diabetic agent with potential anti-aging properties, was repurposed to combat COVID-19 infection also demonstrates antiaging properties.…”

“…The molecular biology behind the tumor reversal process is not only fascinating but alluring. Some chemical compounds used for tumor reversion include LY294002, metformin, sertraline, and ellipticine …”

“…Some chemical compounds used for tumor reversion include LY294002, metformin, sertraline, and ellipticine. 116 Apart from this, T cell therapy such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T cell (CAR-T) therapy may increase the risk of cytokine release resulting in increased severity of COVID-19 infection. Cytokine storm is directly linked to COVID-19-associated diseases such as acute respiratory distress syndrome (ARDS) and multiorgan failure.…”

Antitumor Effect of Traditional Drugs for Neurological Disorders: Preliminary Studies in Neural Tumor Cell Lines

“…Our results showed that levomepromazine and fingolimod were the drugs with a higher antitumor effect reaching an IC50 between 16 and 50 µM in the first case and 16 µM and 23 in the second case, in neural tumor cell lines tested. In the case of levomepromazine, the antitumor activity could be explained by its binding and inhibition of translationally controlled tumor protein (TCTP), which is a novel target for differentiation therapy because it is down-regulated in tumor reversion experiments (Seo and Efferth 2016;Tripathi et al 2021). On the other hand, the fingolimod effect may In addition, the fingolimod cell death mechanism could be related to anoikis as suggested in our results showing detached and rounded cells after treatment.…”

The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer

“…The current knowledge gained from comprehensive preclinical and clinical trials demonstrating a rather limited efficacy of tumor and TME targeted therapies in PDAC patients, leads us to the following assumptions: (i) due to its extraordinary complexity and peculiarity, the TME in PDAC easily compensates pathways, interactions and effects that are modulated by mono-targeted therapies resulting in limited therapeutic efficiency, (ii) targeted therapies applied so far have impaired both tumor-promoting and tumorrestraining TME populations, thereby counteracting the beneficial therapeutic effects albeit it was intended to solely target the tumor-promoting cell populations, (iii) the functional impact of certain host-derived factors on PDAC development and on shaping therapy responses are still insufficiently understood and considered (e.g., the host microbiome) and (iv) the usage of reliable biomarker (not only in tumor tissue but also other compartments) for therapy decision making has still to be improved for treatment of this tumor entity. Accordingly, concepts aiming at restoration and normalization of a physiological, tumor-restraining microenvironment, respectively, rather than at precisely targeting distinct TME components might be more effective strategies [180,310]. For example, Kocher et al focused on the stroma in patients with locally advanced or metastatic PDAC and replenished the Gemcitabine-Nab-Paclitaxel chemotherapy with ATRA in a phase I clinical trial.…”