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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Exploiting nanotechnology to overcome tumor drug resistance: Challenges and opportunities

Ameya R Kirtane1, Stephen M Kalscheuer, Jayanth Panyam

  • 1Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.

Advanced Drug Delivery Reviews
|September 17, 2013
PubMed

Insights

Nanoparticles offer strategies to overcome chemotherapy resistance by targeting efflux transporters. Improving nanoparticle delivery within tumors is crucial for enhancing anticancer drug efficacy against resistant cancers.

Area of Science:

  • Oncology
  • Nanotechnology
  • Pharmacology

Background:

  • Tumor cells develop resistance to chemotherapy through various mechanisms, notably the overexpression of efflux transporters like P-glycoprotein.
  • Efflux transporters reduce intracellular drug concentration, thereby compromising the efficacy of anticancer treatments.
  • Nanoparticle-based strategies are being explored to circumvent efflux-mediated drug resistance.

Purpose of the Study:

  • To review the mechanisms underlying tumor drug resistance.
  • To highlight the potential of nanoparticles in overcoming resistance mediated by efflux transporters.
  • To discuss the challenges and opportunities associated with using nanotechnology against resistant tumors.

Main Methods:

  • Discussion of efflux transporter mechanisms in drug resistance.
  • Review of nanoparticle-based approaches for overcoming efflux-mediated resistance.
  • Analysis of adjunct therapies to improve nanoparticle intratumoral distribution.

Main Results:

  • Overexpression of efflux transporters is a key mechanism of chemotherapy resistance.
  • Nanoparticles can inhibit transporter activity or co-deliver drugs with transporter inhibitors.
  • Poor nanoparticle distribution within tumors can limit treatment effectiveness.

Conclusions:

  • Nanotechnology presents promising avenues for enhancing anticancer drug efficacy in resistant tumors.
  • Adjunct therapies improving intratumoral nanoparticle distribution are vital for successful nanomedicine applications.
  • Further research is needed to optimize nanoparticle delivery and overcome drug resistance.
Keywords:
ABCATP-binding cassetteBCRPCMCCSCsECMEGFEGFREMTEfflux inhibitorsEfflux transportersEndocytosisExcipientsExtracellular matrixGFPHIFHLBHREHRGIFPInterstitial fluid pressureMDRMRPNBDsNPsNanoparticlesP-glycoproteinP-gpPEGPI3KPLGATGF βTMDsTransport barriersTumor penetrationVEGFVEGFRbreast cancer resistance proteincancer stem cellscritical micellar concentrationepidermal growth factorepidermal growth factor receptorepithelial to mesenchymal transitionextracellular matrixgreen fluorescent proteinhistidine rich glycoproteinhydrophilic lipophilic balancehypoxia inducible factorhypoxia responsive elementinterstitial fluid pressuremultidrug resistancemultidrug resistance associated proteinnucleotide binding domainsphosphoinositol-3-kinasepoly(ethylene glycol)poly(lactide-co-glycolide)transforming growth factor βtransmembrane domainsvascular endothelial growth factorvascular endothelial growth factor receptor

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