Drug efflux pumps (ABC transporters)

Molecular pumps on cancer cells that eject chemotherapy and ADC payloads before they can act.

ABCB1 (P-glycoprotein/MDR1), ABCG2 (BCRP), ABCC1 (MRP1). Substrates include taxanes, anthracyclines, MMAE, DXd, SN-38 (ABCG2). Upregulated in mesenchymal and stem-like states. Some newer payloads and radiation are efflux-independent. Pump inhibitors failed clinically due to toxicity.

Resistance: what this kind of term is about · animated schematic, not to scale

Category

Resistance

Connected

technologies

2

Antibody-drug conjugate (ADC)Cytotoxic chemotherapy

drugs

1

ApprovedCytotoxic chemotherapy (taxane)

Cabazitaxel · Jevtana

pathways

5

Drug efflux pumps (ABC transporters)Epithelial–mesenchymal transition & drug efflux KEAP1–NRF2 antioxidant pathway Resistance routes: how a blocked pathway comes back The blood–brain barrier & brain metastasis

terms

10

Blood-brain barrier (BBB)Cell membrane Chemotherapy DXd Hydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)MMAE SN-38 T030 (belotecan derivative)Topoisomerase-I inhibitor payloads Tubulin inhibitor payloads

ideas

4

Combination baskets defined by resistance mechanism rather than by cancer type Efflux-agnostic therapy for mesenchymal TNBC Payload-class switching as the rule for ADC sequencing Sequential multiple-assignment randomised trials to find the best order of ADCs

bottlenecks

1

Acquired resistance to every therapy