Introduction: What they say:
A study from the Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, Jonsson Comprehensive Cancer Center and Broad Stem Cell Research Center, UCLA, Los Angeles, California, USA shows that inhibition of BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma. This study was published in the 9 March 2017 issue of the journal “Cancer Stem Cell” [the number 1 research journal in Stem cell Biology with an I.F of 22.387+] by Prof. Jiong Li, Chen D, and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product-derived Combination therapy for Squamous cell carcinoma of head and neck (HNSCC): A therapeutic mix encompassing a therapeutic mix encompassing Metformin and Navitoclax/ABT-263 inhibits BMI1 and AP-1 expression, overcomes chemotherapeutic resistance, promotes chemosensitivity, suppresses cancer stem cells in HNSCC, and inhibits lymph node metastasis, via down-regulation of its target gene
From Significance of the study to Public health relevance:
Given that: (i) each year nearly 14 million people are diagnosed with cancer globally; (ii) Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer globally;(iii) HNSCC is the third most common cancer in the developing world; (iv) each year nearly half a million people are diagnosed with HNSCC globally; (v) cancer deaths globally are expected to be doubled in a little more than a decades time; and (vi) cancer treatment 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 activate cancer patients’ immune system against tumors (Cancer immunotherapy); (ii) anticancer drugs that target cancer stem cells (CSCs) that aid in tumor relapse, drug resistance and metastasis; (iii) a cheaper alternative to the existing expensive anticancer drugs; (iv) a side-effect-free natural product-based drug; (v) increase the therapeutic index of anti-cancer drugs; and (vi) a way to effectively treat and prevent metastatic progression and relapse of advanced/drug-resistant cancers.
What we infer from what they say:
Prof. Jiong Li’s research team has recently shown that: (1) cancer stem cells (CSCs) are enriched with oncoprotein BMI1 (B cell-specific Moloney murine leukemia virus integration site 1, which promote invasion and lymph node metastasis in HNSCC); (2) BMI1+ CSCs are resistant to anticancer drugs; and (3) BMI1+ CSCs contain increased AP-1 activity that promotes invasion, migration and metastasis of HNSCC. Further, they have shown that inhibition of AP-1 or BMI1: (a) increases chemosensitivity to drug-resistant tumors; (b) inhibits CSCs proliferation; (c) decreases tumor volume; (d) inhibits lymph node metastasis; and (e) eradicates HNSCC metastasis.
From research findings to therapeutic opportunity :
This study suggests, for the first time, a natural product-based combinatorial therapy for HNSCC. A therapeutic mix encompassing Metformin and Navitoclax/ABT-263, by increasing the expression of its target genes, it may decrease the expression of BMI1 and AP-1 expression (fig. 1). Thereby, it may: (i) overcome chemotherapeutic resistance; (ii) promote chemosensitivity; (iii) suppress cancer stem cells proliferation and regeneration in HNSCC; (iv) decrease tumor volume; (v) inhibit lymph node metastasis; (v) inhibit invasion, migration and metastasis. Thus, pharmacological formulations encompassing “Metformin and Navitoclax/ABT-263 or their analogues” (fig. 2) may be used to inhibit metastatic progression of HNSCC.[easy_payment currency=”USD”]
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 and Navitoclax decrease the expression of oncoproteins BMI1 and AP-1?
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Citation: Boominathan, L., Natural product-derived Combination therapy for Squamous cell carcinoma of head and neck (HNSCC): A therapeutic mix encompassing a therapeutic mix encompassing Metformin and Navitoclax/ABT-263 inhibits BMI1 and AP-1 expression, overcomes chemotherapeutic resistance, promotes chemosensitivity, suppresses cancer stem cells in HNSCC, and inhibits lymph node metastasis, via down-regulation of its target genes, 12/February/2017, 10.13 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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