Despite the bulk of data available, surprisingly current knowledge has not yet been developed to a point where HPA-axis reactivity can be rationally exploited for targeted drug treatment, as opposed to the major achievements of drugs targeting the CRH receptors [47].
In summary, this work supports a potentially important role for GSK-3 inhibition in the treatment of pancreatic cancer, but cautions that further work examining the underlying mechanisms is needed for this to be rationally exploited in the clinic.
Since then, methotrexate has been widely used in haematologic and solid cancers, and new generations of antifolates have been rationally designed to exploit multiple aspects of the folate pathway (e.g., raltitrexed in colorectal cancer (Cocconi et al, 1998), and pemetrexed in malignant pleural mesotheliomas (Vogelzang et al, 2003) and non-small-cell lung carcinomas (NSCLC) (Hanna et al, 2004)).
However, as mentioned by the Authors, for various reasons it is difficult or impossible to rationally understand and exploit those models (e.g. "too large" in the case of HumMod, or "not identified" as in the case of Guyton's models of 1972 or 1992).
It derives the basic structure of society from a hypothetical choice situation, the Original Position, in which a veil of ignorance precludes reliance on the contractors' actual limitations – limitations that a Hobbesian contractor might ruthlessly (albeit rationally, if not reasonably) exploit (cf., fn.10).
If placebos could be exploited rationally, perhaps in conjunction with functional drugs, better treatments might be effected.
The development of gunpowder weapons, however, was the first significant success in rationally and systematically exploiting an energy source whose power could not be perceived directly with the ordinary senses.
There are, then, multiple potential sites that rationally could be exploited in developing interventions.
It is possible to exploit these natural mechanisms of cellular uptake with rationally designed reagents.
"But what is important is that we look at the issue rationally, coolly, without hyping up the whole issue, without seeking to exploit it in any way," he said.
