Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

[D.ap]

Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp


ADME

ADME is an abbreviation in pharmacokinetics and pharmacology for "absorption, distribution, metabolism, and excretion," and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug levels and kinetics of drug exposure to the tissues and hence influence the performance and pharmacological activity of the compound as a drug.

P-glycoprotein 1

P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi and bacteria and likely evolved as a defense mechanism against harmful substances.

Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

Background
In US only, the newly diagnosed cancer patient is 1,665,540 every year and the estimated death is 585,720 [1] which are increasing as countries become more developed and more people reach advanced ages. Therefore, many efforts are being done in the war against cancer [2]. One of these efforts is the continuous development of new drugs and forms of chemotherapy.

In cancer, chemotherapy represents the backbone of treatment for many cancers at different stages of the disease. Therefore, chemotherapeutic resistance results in therapeutic failure and usually, (eventually) death. To address these limitations, many researchers focus on how cancer cells manipulate their genomes and metabolism to prevent drug influx and/or facilitate efflux of accumulated drugs, the so called: “the neostrategy of cancer cells and tissues” [3]. In this work, we show that drug resistance is a multifactorial phenomenon that requires attention to the host as well as the tumor and that such factors are organized at different levels (Figure 1).


http://www.cancerci.com/content/15/1/71#B22