Introduction: What they say:
A study from the Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA shows that “FABP4 as a key determinant of metastatic potential of ovarian cancer” This study was published, in the 26 July 2018 issue of the journal “Nature communications” [One of the best journals in biology with an I.F of 12.353], by Prof.Sood AK, Gharpure KM, and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Combinatorial therapy for Metastatic ovarian cancers: A therapeutic mix encompassing Metformin, 17-AAG, Carboplatin, Despiramine, Simvastatin, and Salinomycin (MAAGCDSS) inhibits the expression of FABP4, increases the expression of a number of tumor suppressor genes, and stifles the metastatic potential and the progression of ovarian cancers, via up-regulation of its target gene
The significance of the study to Public health relevance:
Given that: (i) each year nearly 14 million people are diagnosed with cancer globally, and little more than half of them will die due to lack of curative treatment available at present; (ii) cancer deaths globally are expected to be doubled by 2030; (iii) Ovarian cancer not only one among the most common women cancers, but also the one of the most common invasive cancers in women; (iv) Ovarian cancer not only metastasizes frequently, but also relapses; (v) there is an increased incidence of ovarian cancer, as it had caused 113,000 deaths in 1990, while in 2010 160,000 deaths; (vi) it is the fifth leading cause of cancer death in women; (vii) in 2008, cancers of female reproductive organs had caused economic loss of 88 billion US dollars worldwide; and (viii) cancer causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (iii) a side-effect-free natural product-based anticancer drugs that target cancer stem cells; and (iv) a way to effectively treat and prevent metastatic progression and relapse of ovarian cancers.
What we infer from what they say:
FABP4 (fatty acid binding protein) has been shown to be frequently overexpressed in a number of human cancers. However, the molecular gene network that functions downstream of FABP4 is far from understood.
Prof.Sood AK’s research team has recently shown that: (1) FABP4 is overexpressed in ovarian cancers; (2) FABP4 increases the metastatic capability of ovarian cancers; (iii) miR-409-3p inhibits the expression of FABP4; (iv) DOPC nanoliposomes containing either miR-409-3p mimic or FABP4 siRNA stalls ovarian cancer progression in mouse models; and (iv) FABP4 activates both metastatic- and metabolic pathways and thereby contributes to the aggressiveness and poor prognosis of ovarian cancer, suggesting that inhibition of FABP4 may inhibit metabolic and metastatic pathways in ovarian cancer cells and stall the progression of ovarian cancer.
From research findings to therapeutic opportunity :
This study suggests a combinatorial anticancer therapy for high-grade serous metastatic ovarian cancer. A therapeutic mix encompassing Metformin, 17-AAG, Carboplatin, Despiramine, Simvastatin, and Salinomycin (MAAGCDSS), by increasing the expression of its target genes, it may decrease the expression of FABP4 (fig. 1). Thereby, it may: (i) activate the expression of a number of tumor suppressor genes; (ii) inhibit the ovarian cancer stem cell proliferation; (iii) suppress invasion, migration, metastasis, and progression of ovarian cancer; and (iv) promote survival (fig.1). Thus, pharmacological formulations encompassing “Metformin, 17-AAG, Carboplatin, Despiramine, Simvastatin, and Salinomycin (MAAGCDSS) or their analogs,” (fig. 2) may be used to inhibit the progression of metastatic ovarian cancers (fig.3). Finally, depending on the stage of the tumor, level of toxicity, genetic mutations, the molecular signature of the tumors, and the side effects, the anti-cancer drugs, such as Carboplatin and Salinomycin, can be either included in the anti-cancer treatment regimen or excluded.
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.
Undisclosed mechanistic information: How does a therapeutic mix encompassing Metformin, 17-AAG, Carboplatin, Despiramine, Simvastatin, and Salinomycin (MAAGCDSS) inhibit the expression of FABP4 and stall the progression of metastatic ovarian cancers?
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Citation: Boominathan, L., Combinatorial therapy for Metastatic ovarian cancers: A therapeutic mix encompassing Metformin, 17-AAG, Carboplatin, Despiramine, Simvastatin, and Salinomycin (MAAGCDSS) inhibits the expression of FABP4, increases the expression of a number of tumor suppressor genes, and stifles the metastatic potential and the progression of ovarian cancers, via up-regulation of its target gene, 22/August/2017, 7.21 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org
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