Introduction: What they say:
A study from the Division of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; Division of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA shows that inhibition of c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. This study was published in the 20 March 2017 issue of the journal “Nature Medicine” [One of the best journals in General Medicine with an I.F of 30.357 plus] by Prof. Mohammad, Meenu Kesarwani, 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 therapy for enhancing the efficacy of tyrosine-kinase inhibitor (TKI) therapy in BCR-ABL-induced Human leukemia: Salvianolic acid A, one of the main components of Salvia Miltiorrhiza Bunge, decreases the expression of oncoproteins c-FOS, DUSP1 and BCR-ABL, inhibits TKI resistance, restores treatment responsiveness, increases therapeutic index of anticancer drugs, and cure CML and kinase-driven cancers via up-regulation of its target gene[easy_payment currency=”USD”]
From 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; (ii) cancer deaths globally are expected to be doubled by next decade or so; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide; (iv) Acute myeloid leukemia (AML) is one of the most predominant leukemias among all adult leukemias, while Chronic myeloid leukemia (CML) accounts for about only 10% of all leukemias; (v) each year about 10,500 and 2900 new cases of AML are reported in the US and the UK, respectively; (vi) cure rates of AML ranges from 20-45% only, there is an urgent need to find: (i) a way to activate patient’s immune system (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and prevent metastatic progression and relapse of cancers.
What is known:
It has recently shown that: (1) growth factor signalling, mediated by oncoprotein c-fos (FBJ osteosarcoma oncogene) and DUSP1 (dual-specificity phosphatase 1), promotes Tyrosine kinase inhibitor resistance in a number of leukemias, including kinase-driven leukemias; (2) deletion of oncoprotein c-FOS and DUSP1 inhibits CML progression in a BCR-ABL fusion protein kinase–induced mouse model of CML; (3) combined inhibition of c-FOS, DUSP1 and BCR-ABL completely eradicated the tumor cells that cause relapse and drug resistance in a number of mouse models, suggesting that inhibition of oncoproteins c-FOS and DUSP1 may enhance TKI efficacy in treatment-resistant CML and in other kinase-driven leukemias.
From research findings to therapeutic opportunity :
This study suggests a natural product-derived anticancer therapy for enhancing the efficacy of tyrosine-kinase inhibitor therapy in BCR-ABL-induced Human leukemia.
Salvianolic acid A, one of the main components of Salvia Miltiorrhiza Bunge, is known to function as an anticancer agent (fig. 1). However, the detailed mechanistic insights is yet to emerge.
Salvianolic acid A, by increasing the expression of its target genes, it may decrease the expression of c-FOS, DUSP1 and BCR-ABL (fig. 1). Thereby, it may: (i) inhibit growth factor signalling that promote TKI resistance; (ii) eradicate the tumor/cancer stem cells that cause relapse; (iii) eradicate minimal residual disease (MRD); (iv) restore anti-cancer treatment responsiveness; (v) increase therapeutic index of anticancer drugs; (vi) eradicate CML; and (vii) cure CML (fig.1).
Thus, pharmacological formulations encompassing “Salvianolic acid A or its analogues either alone or in combination with other known TKI drugs” may be used to inhibit CML growth.
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Undisclosed mechanistic information: How does Salvianolic acid A decrease the expression of c-FOS, DUSP1 and BCR-ABL to inhibit CML growth?
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Citation: Boominathan, L., Natural product-derived therapy for enhancing the efficacy of tyrosine-kinase inhibitor (TKI) therapy in BCR-ABL-induced Human leukemia: Salvianolic acid A, one of the main components of Salvia Miltiorrhiza Bunge, decreases the expression of oncoproteins c-FOS, DUSP1 and BCR-ABL, inhibits TKI resistance, restores treatment responsiveness, increases therapeutic index of anticancer drugs, and cure CML and kinase-driven cancers via up-regulation of its target gene, 28/March/2017, 2.30 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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