Can cancer drugs help overcome antibiotic resistance?

Can cancer drugs help overcome antibiotic resistance? In a new study published in the Cell journal Chemistry and Biology, Dr. Gerry Wright and colleagues have systematically screened drugs called protein kinase inhibitors and found several candidate compounds that can prevent antibiotic resistance.

With the increased (and almost ubiquitous) use of antibiotics -- from taking antibiotics unnecessarily to fight a virus to the overuse in antibacterial handsoaps -- resistance to we are rapidly running out of effective antibiotics. In an attempt to identify potential new drugs to prevent or overcome such resistance, Dr. Wright’s group tested 80 protein kinase inhibitors, many of which were developed as anti-cancer agents.

So, what’s the connection? Protein kinases are molecules in the cell that respond rapidly to external stimuli. For example, an increase in growth-promoting hormones in the body leads to the activation of protein kinases and results in rapid changes in the cell that leads to growth and proliferation. Protein kinases act as the middle-man that handles the exchange from the outside environment to the response of the cell. Most of the time this is a good thing. It allows for regrowth of skin after wounding and allows for the turnover of the cells in our body to create new ones. Prolonged over-activation of these kinases, however, can be detrimental and is commonly found in cancer cells. New drugs that prevent the activation of these protein kinases (aka protein kinase inhibitors) are being developed to help fight cancers and prevent such growth and proliferation. It turns out that many of these same protein kinases may also be inappropriately activated and therefore contribute to the development of antibiotic resistance. This study sheds some light into new ways to overcome antibiotic resistance.

http://www.cell.com/chemistry-biology/abstract/S1074-5521(11)00411-X

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New vaccines for breast cancer and ebola being developed

Two articles published in this week’s Early Edition of the Proceedings of the National Academies of Science (PNAS) explore the efficacy of new vaccines -- one against the deadly Ebola virus and the second targeting breast cancer tumors. In addition to the reported efficacy of each vaccine, what is interesting about these two papers is that in both cases, the addition of a specific type of adjuvant (an adjuvant is an agent that by itself does little, but when it is given along with a vaccine or drug will improve the efficacy of that drug by inducing a stronger immune response) dramatically improved the responses to the vaccine and produced a therapeutic response. In both studies, the administration of the vaccine alone without the adjuvant did little to induce a response.

Both groups used a protein called the Toll-like receptor (TLR) agonist as the adjuvant of choice. The Ebola vaccine was given with a TLR3 agonist called poly I, poly C or poly I:C, while the breast cancer vaccine was given along with a TLR2 agonist called PamCys. Although use of TLR agonists as cancer vaccine agonists is not a new idea, it is intriguing to see two non-overlapping fields use similar agents to help augment the immune responses and to eliminate a virus or tumor cell. It would seem that TLR adjuvants are very powerful agents to help induce the proper immune response and fight off viral and tumor invasion. Use of similar agents is very disparate diseases bodes well for usefulness of these TLR agonists in therapeutic settings.

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Lakshminarayanan, V et. al. PNAS 2011 Dec 14
http://www.pnas.org/content/early/2011/12/13/1115166109.long

Phoolcharoen, W. et. al. PNAS 2011 Dec 5
http://www.pnas.org/content/early/2011/11/29/1117715108.long

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Bacteria can influence weight

Yet another study has linked the profile of bacteria found in your colon (called the microbiome) to obesity and weight gain. This paper, published in Nature Reviews Endocrinology (7:639-646), reviewed the latest studies to investigate the contribution of bacteria to nutrient metabolism and obesity. Their review has demonstrated that numerous studies have begun to understand the influence of the profile of bacteria in the control of overall weight. Together, all of these studies suggest that the microbiome may be a critical player in metabolism and can influence weight gain or loss.