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:
This study suggests that anti-diabetic drug Pioglitazone may function as an anti-cancer drug in mutant p53 expressing human cancers. Pioglitazone (Actos) 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 Pioglitazone (Actos), by increasing the expression of its target gene, it may increase the expression of tumor/metastasis suppressors genes, such as HNF4α, CADM2, p53, TA-p73, p53, INK4a/ARF and others. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).
Given the ability of Pioglitazone (Actos) to induce the expression of a number of tumor/metastasis suppressor genes, it 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 metastatic cancer patients with Pioglitazone (Actos), 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 Pioglitazone (Actos) increases the expression of tumor suppressor genes, such as HNF4α, CADM2, p53, p53, TAp63, TAp73, INK4a/ARF and others, in mutant p53 expressing cancer cells?
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Awakening the sleeping/cancer-protecting angels in mutant p53-expressing human tumors:
Citation: Boominathan, L., Act(os) against cancer: Pioglitazone (trade name: Actos), an anti-diabetic drug, increases the expression of tumor suppressors genes, such as HNF4α, CADM2, p53, p53, TAp63, TAp73, INK4a/ARF, and others, induces regression of p53-mutated human tumors, via down-regulation of its target gene, 8/September/2018, 12.07 am, Genome-2-Biomedicine Discovery center (GBMD), http://genomediscovery.org
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