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Medical Pharmacology Chapter 33-34: Anticancer Drugs
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Natural Products: Vinca Alkaloids
Overview Continued:
Semisynthetic Vinca Alkaloid Analogues and Derivatives:
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Resistance that develops to the antineoplastic
actions of vinca alkaloid drugs:1
As will be noted in subsequent sections, the various vinca alkaloids exhibit differences in clinical effectiveness and characteristics.1
However, these
agents exhibit cross-resistance.1
Should resistance develop against the antineoplastic activity of one agent, such resistance is likely to apply to other vinca alkaloids as well.9
Antitumor effects of the vinca alkaloids are mediated by a multidrug-resistant system, Pgp, which is also known as the "multidrug-resistant protein 1" or MDR1.9
This system is further described as the "ATP-binding cassette sub-family B member 1.
PgP pumps foreign substances out of cells utilizing an ATP -dependent efflux pump.
Pgp is described as a 170 kDa transmembrane glycoprotein.
Pgp is found in cell types found in liver, kidney, colon, jejunum and pancreas as well as in brain capillary endothelial cells.9
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Abnormalities
in chromosomal structure suggestive of gene amplification with associated
elevated Pgp levels have been described in cells resistant to the action of
vinca alkaloids in cell culture systems.1
Resistance may also occur to the antineoplastic activity of vinca alkaloids due to β-tubulin mutations or in differential β-tubulin isoform expression which prevents effective binding of inhibitors to target sites.1
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