The Ptpn2 pathway blockade enhances the efficacy of Cancer immunotherapy: A therapeutic mix encompassing Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG)  inhibits the expression of protein tyrosine phosphatase PTPN2, increases interferon-IFNγ signaling, augments antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival, via up-regulation of its target gene, 25/February/2019, 1.17 am

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Introduction: What they say:

A recent study from Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; and Division of Pediatric Hematology and Oncology, Children’s Hospital, Boston, Massachusetts 02115, USA has identified Ptpn2 as a cancer immunotherapy target. This study was published, in the July 2017 issue of Nature (one of the best journals in General science with an impact factor of 43 plus), by Prof Haining WN, Manguso and others


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: The Ptpn2 pathway blockade enhances the efficacy of Cancer immunotherapy: A therapeutic mix encompassing Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG)  inhibits the expression of protein tyrosine phosphatase PTPN2, increases interferon-IFNγ signaling, augments antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival, via up-regulation of its target gene


From Significance of the study to Public health relevance: 

Given that: (i) PD-1 checkpoint blockade is effective only in minority of cancer patients; (ii) each year nearly 14 million people are diagnosed with cancer globally; (iii) cancer deaths globally are expected to be doubled in the next decade; (iv) metastasis is the principle reason for most of the cancer deaths; (v) 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 patients’ immune system against tumors (Cancer immunotherapy); (ii) a way to improve the efficacy of immunotherapy by targeting a number of immune evasion molecules simultaneously; (iii) anti-cancer drugs that target cancer stem cells that aid in tumor relapse and resistance; (iv) anti-cancer drugs that target cell adhesion molecules that aid in metastatic spread; (v) a cheaper alternative to the existing expensive anticancer drugs; (vi) a side-effect-free natural product-based drug; (vii) increase the therapeutic index of anti-cancer drugs; and (viii) a way to effectively treat and prevent metastatic progression and relapse of advanced/drug-resistant cancers.


What is known?

It has recently been shown that blocking immune evasion molecules, including cell surface receptor PD-1, with antibodies, one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year recently.


From Research Findings to Therapeutic opportunity:

 A therapeutic mix encompassing Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG), by increasing the expression of its target gene, it may decrease PTPN2/TC-PTP expression. Thereby, it may: (i) diminish the expression of a number of immune evasion molecules in cancer cells; (ii) increase IFNγ signaling; (iii) increase antigen presentation; (iv) augment unfolded protein response: (v) increase the number of tumor-infiltrating immune cells; (vi) augment T-cell anti-tumor immunity; (vii) decrease tumor burden and promote growth suppression; (viii) increase survival of patients with cancers; and (ix) increase the efficacy of immunotherapy (fig. 1).

Figure1. Mechanistic insights into how a therapeutic mix encompassing Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG)  enhances the efficacy of Cancer Immunotherapy. MNDDG, by increasing the expression of its target genes, it promotes the expression of a number of tumor suppressor genes, inhibits the expression of a number of immune invasion molecules, including PTPN2//TC-PTP, augments T-cell mediated anti-tumor immunity and attenuates tumor growth

Figure 2. A therapeutic mix encompassing Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG) enhances the efficacy of cancer immunotherapy through down-regulation of PTPN2.

Thus, pharmacological formulations encompassing “Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG) or their analogs, either alone or in combination with any of the known anticancer agents,“ may be used to (i) inhibit the progression of tumors; and (ii) enhance the efficacy of Cancer Immunotherapy. [easy_payment currency=”USD”]


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.

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

Amount: $750#

Undisclosed mechanistic information: How does MNDDG suppress the expression of PTPN2/TC-PTP?

For purchase and payment details, you may reach us at admin@genomediscovery.org

# Research cooperation


References:

Citation: Boominathan, L., The Ptpn2 pathway blockade enhances the efficacy of Cancer immunotherapy: A therapeutic mix encompassing Metformin, Navitoclax, dasatinib, 2-deoxy-d-glucose (2DG) (MNDDG)  inhibits the expression of protein tyrosine phosphatase PTPN2, increases interferon-IFNγ signaling, augments antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival, via up-regulation of its target gene, 25/February/2019, 1.17 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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

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