Combinatorial anti-cancer therapy blocking GPC2 pathway and immune receptors enhances the efficacy of Cancer immunotherapy in Neuroblastoma: A therapeutic mix encompassing   Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG)  inhibits the expression of GPC2, increases IFNγ signalling, increases antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, inhibits neuroblastoma proliferation, decreases tumor burden and increases survival via up-regulation of its target gene, 28/February/2019, 8.23 am

Probiotics function as anti-HIV agents: Probiotic Bacillus subtilis B10 increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production, via upregulation of its target gene, 28/February/2019, 8.09 am
February 28, 2019
Probiotic Bacillus subtilis B10-based antiviral therapy for chikungunya (CHIKV) and Zika (ZIKV) viruses: Probiotic Lactobacillus Rhamnosus increases spermidine/spermine N1-acetyltransferase (SAT) expression, depletes spermidine and Spermine levels, and restricts Chikungunya and Zika viruses replication via upregulation of its target gene, 28/February/2019, 8.35 am
February 28, 2019
Show all

National Science day special

*********

We wish everyone a very happy national science day. On this special occasion, we are happy to announce that Bio-Med/Pharma/Therapeutic/Clinical ideas posted today (28/February/2019) will be available to the use of Scientists/Professors/Faculties/Teachers/Physicians/Researchers for free. So, there will be no terms and conditions for the ideas posted today. Each idea posted will be served first come, first serve basis. Write to admin@genomediscovery.org for more details.

Dr L Boominathan PhD

President, Director & CSO, GBMD.

_________________________________________________________________________________________________________________________________________________

 

Introduction:What they say:

A recent study from Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA shows that “Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma”. This study was published, in the September 2017 issue of Cancer cell (one of the best journals in Cancer biology with an impact factor of 28 plus), by Prof Maris JM, Bosse 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 anti-cancer therapy blocking GPC2 pathway and immune receptors enhances the efficacy of Cancer immunotherapy in Neuroblastoma: A therapeutic mix encompassing   Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG)  inhibits the expression of GPC2, increases IFNγ signalling, increases antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, inhibits neuroblastoma proliferation, 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) neuroblastoma accounts for about 7-10% of childhood cancer; (ii) the chances of survival of children diagnosed with high risk glioblastoma are less than 50%; (iii) the molecular pathways involved in the development of Neuroblastoma are not very well understood yet; (iv) blockade of immune evasion molecule such as PD-1 is effective only in minority of cancer patients; (iv) each year nearly 14 million people are diagnosed with cancer globally;  (v) cancer deaths globally are expected to be doubled in the next decade; (vi) metastasis is the principle reason for most of the cancer deaths; (vii) 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 effectively activate patients’ immune system against tumors (Cancer immunotherapy); (ii) a way to improve the efficacy of immunotherapy by targeting more immune evasion molecules at a time; (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 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.

Prof Maris JM’s research team has shown recently that: (i) compared to normal tissues GPC2 [Glypican 2] protein is abnormally expressed in neuroblastoma; (ii) proto-oncogene MYCN increases the expression of GPC2; (iii) somatic gain of the GPC2 locus also aids in abnormal expression of GPC2 in neuroblastoma; (iv) GPC2 augments neuroblastoma cell proliferation; and (v) an antibody-drug conjugate directed against GPC2 protein is cytotoxic to neuroblastoma cells, suggesting that inhibition of cell surface GPC2 may enhance the efficacy of cancer immunotherapy.


From Research Findings to Therapeutic opportunity:

therapeutic mix encompassing  Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG), by increasing the expression of its target gene, it may decrease GPC2 expression (fig. 1). Thereby, it may: (i) diminish the expression of a number of immune evasion molecules in cancer cells; (ii) increase IFNΥ signaling; (iii) increase antigen presentation; (iv) augment unfolded protein response: (v) increase the number of tumor-infiltrating immune cells; (vi) increase T-cell anti-tumor immunity; (vii) inhibit neuroblastoma proliferation; (viii) decrease tumor burden and promote growth suppression; (ix) increase survival of patients with neuroblastoma; and (x) increase the efficacy of immunotherapy (fig. 1).

Figure 1. Mechanistic insight into how MNDDG enhances the efficacy of cancer immunotherapy in neuroblastoma. ADDF, by down regulating the expression of immune evasion molecule GPC2, among others, in cancer cells, it augments T-cell mediated anti-tumor immunity

Figure 2. A therapeutic mix encompassing  Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG) functions as an anti-cancer agent through down regulation of GPC2

 

Thus, pharmacological formulations encompassing “A therapeutic mix encompassing  Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG)  or their analogues”, either alone or in combination with other drugs, may be used to (i) inhibit the progression of neuroblastoma; 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 a therapeutic mix encompassing   Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG) suppresses the expression of GPC2 and augments anti-tumor immunity

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

# Research cooperation


References:

Citation: Boominathan, L., Combinatorial anti-cancer therapy blocking GPC2 pathway and immune receptors enhances the efficacy of Cancer immunotherapy in Neuroblastoma: A therapeutic mix encompassing   Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG)  inhibits the expression of GPC2, increases IFNγ signalling, increases antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, inhibits neuroblastoma proliferation, decreases tumor burden and increases survival via up-regulation of its target gene, 28/February/2019, 8.23 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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

Courtesy: When you cite drop us a line at info@genomediscovery.org

 

 

 

Comments are closed.