Re: What makes a drug a good anticancer drug? [00015] Medicine On Line


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Re: What makes a drug a good anticancer drug?



>Ok...  Here we go.  I am giving a speech on some research done 
>by
>Dr. Farrell and some of his dinuclear platinum complexes.  I am 
>having
>some real problems understanding some things.  What needs to be 
>looked
>at in order to determine if a drug is a good anticancer drug.
>In his paper he looks at : DNA Unwinding, DNA-DNA Interstrand 
>Cross-Linking,
>Adduct formation and Sequence Specificity for Dinuclear 
>Platinum Complexes,
>(Pt, Pt) Intrastrand Cross-links.
>
>What I would like to know is what kind of results is he looking 
>for
>inorder to determine that the complexes are good anticancer 
>drugs?
>Example: something is "very effcient cross-linking agent" ---> 
>so what
>         does this tell me?

A good cancer drug is one that targets the cancer and kills it efficiently 
(and 100%) with minimal short or longterm complications to the "normal" cells.
The cancer drug should be able to able to reach the cancer cells (good 
penetration) where ever they may be, be stable prior to their entry into the 
cell to do their dirty work...and then be rapidly removed from the body when 
they are done. The action should be fairly fast and well-targeted...so any 
cancer cells remaining cannot devise methods to side-step the chemo's action 
(called chemoresistance).

This is a clinical definition...and not a basic science answer...

>
>Also why does he look at B-->Z induction (what is it?), 
>unwinding angle.

There are several different configations (think topology) of DNA. The DNA coils 
can change from one form to another. The B and Z forms are crystallographic 
(x-ray structure) definitions...

Cancer drugs work in a varity of ways. Drugs such as taxol, taxotere, navelbine 
work by binding to the tubulin monomer composing the mitotic apparatus of the 
dividing cell...freezing ALL dividing cells into the process. Other drugs, such 
as CPT-11, topotecan, etc work by screwing up the unwinding of the DNA from its 
supercoiled state to the linear state needed for transcription and 
translation. Remember, DNA must be in a linear state to be translated into 
RNA...as well as to be duplicated for cell division.

Other drugs, such as cisplatin, carboplatin, etc. bind to specific locations on 
the DNA strand and make the DNA not useable. Some agents, such as 
5-fluorouracil (5FU) are mistaken by the  rapidly growing cancer cell and 
incorporated into the new DNA...and screw up the daughter cells.

Other forms of chemo involve hormone blockage treatments. Some forms of cancer, 
such as some breast and prostate cancer, experience accelerated growth in the 
presence of estrogen or testosterone (respectively)...so if the individual is 
treated with a drug that binds to the tumor cell's hormone receptors...thus 
'gumming up the works' by occupying the receptor...the cell stops growing. It 
may not kill the cancer...but it stops growing.

You might wish to read the summary chapters in Devito et al.'s "Cancer: 
Principles and Practices of Oncology" to get a feel for how chemo works in 
general.

Do you have a specific question?

--
E. Loren Buhle, Jr., Ph.D          INTERNET: BUHLEL01@MCRCR6.MED.NYU.EDU
*** The views expressed here are mine and do not reflect the views or
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