Introduction:What they say:
A recent study from Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA shows that “Deubiquitination and Stabilization of PD-L1 by CSN5.” This study was published in the 12 December 2016 issue of Cancer cell (one of the best journals in Cancer Science with an impact factor of 23.523) by Prof Mien-Chie Hung, Lim SO 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 PD-L1 pathway blockade enhances the efficacy of Cancer immunotherapy: Atorvastatin, one of the widely used lipid-lowering drug, inhibits the expression of PD-L1, inhibits inflammatory signalling and the number of tumor-infiltrating lymphocytes and macrophages, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival via up-regulation of its target gene
What is known?
It has recently been shown that blocking cell surface receptor PD-1/CD274 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:
Atorvastatin (trade name: Lipitor/Atorva), an HMG-CoA reductase inhibitor and a lipid-lowering drug, is primarily used in the treatment of Cardiovascular disease; and is one of the best selling drugs in the US whose sales has crossed $125 billion from 1996-2012.
Here, I present data which suggests that Atorvastatin may function as an anticancer agent by enhancing the efficacy of cancer immunotherapy.
Atorvastatin, by increasing the expression of its target gene, it may ubiquitinate and destabilize PD-L1/CD274 (fig. 1). Thereby, it may: (i) diminish PD-L1 expression in cancer cells; (ii) inhibit inflammatory TNFα signaling; (iii) decrease the number of tumor-infiltrating lymphocytes and macrophages; (iv) increase T-cell anti-tumor immunity; (v) decrease tumor burden; and (vi) increase survival of patients with breast cancer (fig. 1).
Figure 1. Mechanistic insight into how Atorvastatin (trade name: Lipitor/Atorva) enhances the efficacy of cancer immunotherapy. Atorvastatin, by decreasing the expression of PD-L1 in cancer cells, it augments T-cell mediated anti-tumor immunity
Thus, pharmacological formulations encompassing “Atorvastatin or its analogues or Atorvastatin in combination with other drugs“ may be used to (i) inhibit the progression of tumors; and (ii) enhance the efficacy of Cancer immunotherapy.
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Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Amount: $100
Undisclosed mechanistic information: How Atorvastatin suppresses the expression of PD-L1 and augments anti-tumor immunity
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References:
Citation: Boominathan, L., The PD-L1 pathway blockade enhances the efficacy of Cancer immunotherapy: Atorvastatin, one of the widely used lipid-lowering drug, inhibits the expression of PD-L1, inhibits inflammatory signalling and the number of tumor-infiltrating lymphocytes and macrophages, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival via up-regulation of its target gene, 13/February/2017, 2.15 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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