For example, we know that when patients are exposed to a new medication (ie. chemotherapy drug), some patient will have inherent resistance to the drug. That is they are promptly rejecting the drug, while other will respond first and then develop mechanisms of resistance. To date, they are no ways of determining which patient is doing what when exposed to the drug! And this despite our advances in technology.
Our current practice is to give the drug, and wait 3-6 months and check through radiologic and biomarker means if the tumor grow despite the drug. During the 3 to 6 months, refractory tumors have time to build in new genetic mutations giving them new mechanisms of escape, defense and otherwise eluding future attacks, and most importantly metastasize to new sites in the host, complicating our battle and making full eradication impossible and dooming our chance for a cure! Indeed with tumors of "aggressive" tendencies, 6 months is a lifetime of opportunities to settle in and impose a toll of reversible and irreversible disruptions into the host!
This strategy is not good for us.
This is happening despite our knowledge of many facts that could help us avoid this current practice. we know already many pathways and mechanisms of resistance (ie. the MDR gene) but we don't use them for our relevant patients. We try it on dogs however!
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"Get Your Dog Tested*
Blood sample or cheek swab?
DNA obtained from a dog’s blood is the same DNA that would be obtained from that dog’s cheek cells using a swab. We allow submission of either sample because blood is often the sample preferred by veterinary hospitals while cheek swabs are generally preferred by dog owners."College of Veterinary Medicine
Veterinary Clinical Pharmacology Lab
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We know that pathways get underway through consumption of measurable co-factors and obligatory steps that we can promptly measure and determine that the drug is being used or allowed to act at cellular level. Is it the lack of will, or the sense of desperation because of limitations in our available options that make us afraid to know the truth early. The point is we cannot go on avoiding to know what is in store for the patients!
Many drugs act through Adenyl Cyclase, many drugs use the Gerb-2, Gab1, etc....why can't we use these available biomarkers of drug actions. DNMT1 AT EPIGENETIC LEVEL (OR SIMILAR MOLECULES)
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DNA (cytosine-5)-methyltransferase 1 is an enzyme that in humans is encoded by the DNMT1 gene.[1]
DNA (cytosine-5-)-methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.[2][3]" wikipedia
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has been proposed as a way to gauge imprinted information
can we try this as a biomarker of drug effect?
SUFFICE IS TO SAY WE CAN'T GO ON FOOLING OUR PATIENTS INTO INEFFECTIVE DRUG TRIALS! THE TIME TO KNOW IS NOW! AND HERE WE GO AGAIN, A TEAM OF INVESTIGATORS WITH SOPHISTICATED MACHINES NEED TO GO BACK TO WORK AGAIN ON THIS NEW LEAD! THE ANSWER IN 5 YEARS!
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