Some cancer cells pump drugs out
How ABC transporters pump chemotherapy drugs out of cancer cells, why this causes multidrug resistance, and the early-stage research into quercetin as a possible pump modulator.
Page 4 of the hub that unpacks the 2026 Cancer Stem Cells and Drug Resistance Review.
Some cancer cells can reduce the amount of drug that stays inside them. Imagine a treatment drug entering a cancer cell, only for the cell to keep shuttling it back out through tiny molecular exit pumps in its outer membrane.
These are called ATP-binding cassette (ABC) transporters. They use cellular energy to export a wide range of substances—including some anticancer drugs—before enough medicine remains inside the cell to do its job.
The three transporters most often discussed in cancer-drug resistance are
ABCB1 (also called P-glycoprotein or MDR1)
ABCG2 (also called breast cancer resistance protein, or BCRP)
ABCC1 (also called multidrug-resistance-associated protein 1, or MRP1)
Why is multi-drug resistance is such a complex challenge?
This field is especially challenging because these pumps are not selective for just one medicine. Depending on the transporter and tumour type, they can affect drugs from several classes, including:
Anthracyclines, such as doxorubicin.
Taxanes, such as paclitaxel and docetaxel.
Vinca alkaloids.
Topoisomerase inhibitors, such as etoposide or topotecan.
Some targeted medicines.
The term multi-drug resistance: a cancer that has increased one or more efflux pumps may become less sensitive to several different treatments at the same time—not necessarily because every treatment was wrong, but because less of the active drug is staying inside the cancer cells.
For people who have been through several lines of treatment, this biology can help make sense of a frustrating experience: a drug may look appropriate on paper, and may even have caused an initial response, yet later become less effective.
Pump-mediated resistance is only one possible reason; cancer can also evolve new mutations, activate alternative survival pathways, become protected by its microenvironment or change into a more treatment-tolerant cell state.
The review's key point is that resistance is usually a network, not one faulty switch.
Why can't doctors simply turn the pumps off?
These transporters are not unique to cancer. They help protect normal tissues, including the intestine, liver, kidneys and the blood–brain barrier, by moving potentially harmful substances and medicines through or out of cells.
Earlier attempts to block P-glycoprotein and related pumps often required doses that caused side effects or changed the way chemotherapy was absorbed, metabolised and cleared from the body—sometimes raising drug levels in normal tissues as well as tumours. Even newer, more specific pump inhibitors have not yet produced a broadly successful standard treatment strategy.
Where the research is heading
Rather than relying on one "pump blocker," researchers are investigating more selective approaches: identifying which cancers genuinely depend on particular transporters; designing medicines or drug payloads that are less easily exported; using targeted delivery systems such as nanoparticles or antibody–drug conjugates; and combining treatments that attack several resistance routes at once.
These are active research directions, not established self-treatment strategies. Antibody–drug conjugates can be highly effective in selected cancers, but they too may eventually encounter resistance through altered targets, drug release or efflux pumps—another reason cancer treatment needs to be tailored and continually reassessed.
A useful question for the treatment team: "Given my cancer type and the treatments I have already had, is there a known resistance pattern that could influence the next treatment choice, molecular testing or clinical-trial options?"
A natural compound research lead: quercetin and drug-efflux pumps
Quercetin has been studied as a possible way to interfere with the "pump drugs out" resistance mechanism. In laboratory models—not in proven patient treatment—quercetin has reduced the expression and/or activity of transporters including ABCB1/P-glycoprotein, ABCC1/MRP1 and ABCG2/BCRP, allowing more of a test drug to remain inside resistant cancer cells.
For example, in daunorubicin-resistant pancreatic-cancer cell lines, quercetin changed P-glycoprotein function and reduced ABCB1 expression; in a resistant gastric-cancer model, it reduced MRP1/ABCC1 and increased sensitivity to 5-fluorouracil and doxorubicin.
This is an interesting proof-of-concept, particularly because ABC pumps are relevant to multidrug resistance and stem-like cancer-cell states. But it is not evidence that quercetin supplements reverse chemotherapy resistance in people: effective human dose, formulation, timing, drug interactions and effects on normal protective transporters are unresolved. Quercetin should only be added when an oncology pharmacist and treating oncologist have reviewed the exact product and regimen.
A research lead: quercetin and drug-efflux pumps. Quercetin, a flavonoid found in foods such as onions, apples, berries and tea, has been studied as a possible way to interfere with the "pump drugs out" resistance mechanism. In laboratory models—not in proven patient treatment—quercetin has reduced the expression and/or activity of transporters including ABCB1/P-glycoprotein, ABCC1/MRP1 and ABCG2/BCRP, allowing more of a test drug to remain inside resistant cancer cells.
For example, in daunorubicin-resistant pancreatic-cancer cell lines, quercetin changed P-glycoprotein function and reduced ABCB1 expression; in a resistant gastric-cancer model, it reduced MRP1/ABCC1 and increased sensitivity to 5-fluorouracil and doxorubicin. This is an interesting proof-of-concept, particularly because ABC pumps are relevant to multidrug resistance and stem-like cancer-cell states. But it is not evidence that quercetin supplements reverse chemotherapy resistance in people: effective human dose, formulation, timing, drug interactions and effects on normal protective transporters are unresolved.
Quercetin should therefore be considered a research discussion—not an add-on to treatment—unless an oncology pharmacist and treating oncologist have reviewed the exact product and regimen.[
Further reading:
Hamdy H, Li Y, Li C, et al. Cancer stem cells and drug resistance in cancer: molecular mechanisms and therapeutic targets. Molecular Biomedicine. 2026;7:114. https://doi.org/10.1186/s43556-026-00516-2[ppl-ai-file-upload.s3.amazonaws][link.springer]
Quercetin and multi-drug resistance research
Quercetin as a Potential Modulator of P-Glycoprotein Expression and Function in Cells of Human Pancreatic Carcinoma Line Resistant to Daunorubicin Molecules. 2010;15(2):857–870. https://doi.org/10.3390/molecules15020857 https://pubmed.ncbi.nlm.nih.gov/20335952/ [pubmed.ncbi.nlm.nih]
Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric Adenocarcinoma AGS Cells International Journal of Molecular Sciences. 2018;19(4):1066. https://pmc.ncbi.nlm.nih.gov/articles/PMC6017870/ [pmc.ncbi.nlm.nih]
Reversal of Multidrug Resistance in Cancer by Multi-Functional Flavonoids Frontiers in Oncology. 2019;9:487. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00487/full This is a review rather than a clinical trial; useful for its summary of laboratory findings involving quercetin, ABCB1, ABCC1 and ABCG2.[frontiersin]
This information is for education only. It is not medical advice, diagnosis, or treatment. Please speak with a qualified clinician before making changes to care, medication, or supplement use.
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