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You found certain cancer cells develop a drug resistance towards a chemotherapeutic medicine. You further found much higher expression of an ABC superfamily transport protein in those cells compared to drug-sensitive cells. You will expect:

A. There is higher concentration of the medicine inside drug-resistant cells than in drug-sensitive cells.
B. No intracellular concentration of the medicine will be observed in drug resistant and drug-sensitive cells.
C. Removing the ATPase domain of the transporter will not affect the intracellular concentration of the medicine.
D. Treating the cells with another structurally irrelevant drug may still kill the cancer cells.

User Tomas Vana
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1 Answer

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Final answer:

Cancer cells with drug resistance often express efflux pumps that lower the intracellular concentration of chemotherapeutic drugs.

Step-by-step explanation:

If you found that certain cancer cells develop a drug resistance towards a chemotherapeutic drug and have a higher expression of an ABC superfamily transport protein compared to drug-sensitive cells, you would expect that the concentration of the medicine inside drug-resistant cells would be lower, not higher, than in drug-sensitive cells.

This is because such transport proteins often act as efflux pumps to actively transport the drug out of the cell, preventing the accumulation of the drug to cytotoxic levels. Therefore, option A is incorrect.

Option B suggests that there would be no intracellular concentration of the medicine observed in either cell type, which is not true and thus incorrect. Intracellular concentration would be expected, albeit lower in drug-resistant cells due to the action of the efflux pumps.

For option C, if you were to remove the ATPase domain of the transporter, this would affect the intracellular concentration of the medicine because ATPases provide the energy needed for the active transport process carried out by these efflux pumps.

Without this domain, the pump would not function properly to remove the drug, leading to a higher intracellular concentration of the medicine in the drug-resistant cells. Option C, therefore, is also incorrect.

Regarding option D, treating the cells with another structurally irrelevant drug may or may not be successful depending on whether the efflux pump recognizes and transports that drug. The multi-drug resistance (MDR) efflux pumps can eliminate many different drugs, suggesting option D is a possibility.

Therefore, treating with a structurally unrelated drug might overcome resistance if the pump does not recognize or transport the new drug efficiently. Option D can be correct in the context of designing a therapeutic strategy that circumvents the efflux pump resistance mechanism.

User Dhondup
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