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Awakening the sleeping/cancer-protecting angels in mutant p53-expressing human tumors: Sitagliptin (trade name: Januvia), a DPP4 inhibitor, increases the expression of tumor suppressors genes, such as  BTG2, INK4a, TA-p73, TAp63, p53, and others, induces regression of p53-mutated human tumors, via down regulation of its target gene, 22/June/2018, 2.54 pm

Unknown function of a known drug in the treatment of muscle atrophy and wasting: Simvastatin(brand name: Zocor),  a lipid-lowering agent,  increases the expression of FGF19 and its receptor ß-Klotho, phosphorylates ERK1/2 and S6K1, decreases the expression of tumor suppressors  genes, promotes regeneration of muscle cells and hypertrophy of skeletal muscle, and reverses muscular atrophy and wasting via up regulation of its target gene, 22/June/2018, 2.50 pm
June 22, 2018
Unearthing an unknown function of a  known drug in regenerative muscle atrophy: Simvastatin(brand name: zocor), a lipid-lowering medication, increases the expression of IGF-1, PI3K(p85a) and B-Myb, decreases the expression of tumor suppressors, promotes regeneration of muscle cells, and reverses muscle atrophy via up regulation of its target gene, 22/February/2018, 3.04 pm
June 22, 2018
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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:  

The antihyperglycemic agent Sitagliptin has been shown to decrease breast/prostate cancer risk in patients with TIIDM. However, the mechanism of action remains unknown.

This study suggests that Sitagliptin (brand name: Janavi) may function as an anti-cancer/metastasis agent by increasing the expression a number of tumor/metastasis suppressor genes.  Sitagliptin, by increasing the expression of its target gene, it may increase the expression of tumor/metastasis suppressors genes, such as TIMP3, CCM3/KRIT1, TA-p73, TAp63, p53, and others. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).

Figure 1. Mechanistic insight into how anti-diabetic drug Sitagliptin functions as an anticancer/antimetastatic agent in mutant p53-expressing tumors.  Sitagliptin,  by activating tumor/metastasis suppressor genes, such as BTG2, INK4a, TA-p73, TAp63, p53 and others, in  metastatic tumors, it may inhibit the progression of mutant-p53 expressing human cancers.


Therapeutic opportunity:

Given the ability of Sitagliptin 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 terminally ill metastatic cancer patients with sitagliptin, as it may stall the progression of advanced metastatic cancers. Given its low cost compared to other anti-cancer/metastatic agents, it may be a prefered anti-cancer/metastatic agent.


Details of the research findings

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $300#

Undisclosed mechanistic information: How sitagliptin increases the expression of tumor suppressor genes, such as BTG2, INK4a, TA-p73, TAp63, p53, and others,  in mutant p53 expressing cancer cells?

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References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L., Awakening the sleeping/cancer-protecting angels in mutant p53-expressing human tumors: Sitagliptin (trade name: Januvia), a DPP4 inhibitor, increases the expression of tumor suppressors genes, such as  BTG2, INK4a, TA-p73, TAp63, p53, and others, induces regression of p53-mutated human tumors, via down regulation of its target gene, 22/June/2018, 2.54 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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