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: Natural product-based PD-1 pathway blockade for Human cancer therapy: Lovastatin, a cholesterol lowering drug, decreases the expression of Glycogen synthase kinase-3β, 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.
Research Findings:
A number of studies suggests that Lovastatin, a commonly used drug in the treatment of hypercholesterolemia, inhibits tumor cell proliferation. However, the mechanism of action is far from clear.
Figure 1. Lovastatin ((Merck’s Mevacor). Lovastatin, found in Pu-erh Tea, enhances cytolytic function of Cytotoxic T-lymphocytes, augments anti-tumor activity, and inhibits metastatic cancer progression via downregulation of Glycogen synthase kinase-3β and PD-1
This study suggests, for the first time, that Lovastatin, by regulating the expression of its target gene, it may suppress the expression of Glycogen synthase kinase 3-β. Thereby, 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.
Therapeutic opportunity:
Thus, pharmacological formulations encompassing “Lovastatin or its analogues, either alone or in combination with other antic-cancer drugs drugs” may be used to inhibit the progression of tumors; and the efficacy of cancer immunotherapy.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Amount: $50#
Undisclosed information: How Lovastatin suppresses the expression of PD-1 and augments anti-tumor immunity
# Research cooperation
References:
Citation: Boominathan, L., Natural product-based PD-1 pathway blockade for Human cancer therapy: Lovastatin, a cholesterol lowering drug, decreases the expression of Glycogen synthase kinase-3β, 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, 1/September, 2017, 10.53 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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