Introduction:What they say:
A recent study from Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK shows that “Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.” This study was published in the 16 February 2016 issue of Immunity (one of the best journals in Immunology with an impact factor of 20+) by Prof Rudd CE, Taylor A and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Small molecule-based PD-1 pathway blockade for Human cancer therapy: Lovastatin (brand name: Mevacor), a hypolipidemic agent, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene
What is known?
It has recently been shown that blocking 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 a few years ago.
From Significance of the study to Public health relevance:
Given that: (i) each year nearly 14 million people globally are diagnosed with cancer, and a little more than half of them will die; (ii) cancer deaths globally are expected to be doubled by 2030; (iii) 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 prevent an individual from being susceptible to cancer by strengthening his/her own immune system; (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.
This study suggests a small molecule-based Human cancer immunotherapy. Lovastatin (brand name: Mevacor), a statin drug used in the treatment of hypercholesterolemia, has been shown to function as an anticancer agent in a number of cancers, including Triple-negative breast cancer (TNBC). However, the detailed mechanism of action is yet to emerge.
The study presented here suggests that, Lovastatin, by decreasing the activity of its target gene, it may: (a) increase transcription factor T-bet expression; (b) inhibit co-inhibitory receptor PD-1 expression; (c) increase CD8(+) cytotoxic T lymphocyte function; (d) augment anti-tumor activity; & (e) inhibit metastatic cancer progression.
Thus, pharmacological formulations encompassing “Lovastatin or its analogues or Lovastatin plus any of the known anti-cancer agents” may be used to inhibit the progression of tumors.
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/
Undisclosed mechanistic information: How Lovastatin suppresses the expression of PD-1 and augments anti-tumor immunity
# Research cooperation
Citation: Boominathan, L., Small molecule-based PD-1 pathway blockade for Human cancer therapy: Lovastatin (brand name: Mevacor), a hypolipidemic agent, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene, 8/January/2017, 10.46 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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