From Significance of the study to Public health relevance:
Given that: (1) cancer suppressor p53 is mutated in more than 50% of human cancers of different tissue origin; (2) p53 pathway is altered in about 80% of tumors.; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in mutant p53-overexpressing tumors; (4) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (5) cancer causes the considerable economic loss worldwide, there is an urgent need to find: (i) a cheaper alternative to the existing expensive drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and stall metastatic progression and relapse of mutant p53-overexpressing human cancers.
From therapeutic strategy to Research Findings:
(i) Therapeutic strategy:
This study suggests a therapeutic strategy for stalling the progression of p53-deficient/deleted or mutant-p53 expressing metastatic cancers. By activating tumor suppressor p53’s unmutated “homologous protein such as TAp73/p63” in p53-deficient or mutant-p53 expressing metastatic cancer cells, one can stall their progression.
(ii) Research findings:
PCGF2/Mel-18 has been shown to function as a tumor suppressor in a number of cancers. However, the mechanism of action remains largely unknown.
This study suggests that PCGF2/Mel-18 may function as an anti-cancer/metastasis agent by increasing the expression a number of tumor/metastasis suppressor genes.
PCGF2/Mel-18, by increasing the expression of its target gene, it may increase the expression of tumor/metastasis suppressors genes, such asSMAD7, p12DOC1/CDK2AP1, TA-p73, TAp63, p53, and others. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).
Given the ability of PCGF2/Mel-18 to induce the expression of a number of tumor/metastasis suppressor genes, its activators or inducers may be used, either alone or in combination with other anticancer drugs, to inhibit the progression of p53-mutated invasive metastatic tumors. Taken together, this study suggests, for the first time, that oncologists may consider treating terminally ill metastatic cancer patients with PCGF2/Mel-18 inducers, as it may stall the progression of advanced metastatic cancers. (figure 2).
Details of the research findings:
Idea Proposed/Formulated by Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How PCGF2/Mel-18 increases the expression of tumor suppressor genes, such as SMAD7, p12DOC1/CDK2AP1, TA-p73, TAp63, p53, and others, in mutant p53 expressing cancer cells?
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Citation: Boominathan, L., Awakening the sleeping/cancer-protecting angels in mutant p53-expressing human tumors: PCGF2/Mel-18 increases the expression of tumor suppressors genes, such as SMAD7, p12DOC1/CDK2AP1, INK4a/ARF, TA-p73, TA-p63, p53, and others, induces regression of p53-mutated human tumors, via down-regulation of its target gene, 18/September/2018, 9.05 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org
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