Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine

Pharmaceutical Research
Minjee KimWilliam F Elmquist

Abstract

The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously "leaky" BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of "active, free drug" to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient's tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases.

References

Feb 22, 1990·The New England Journal of Medicine·R A PatchellB Young
Jul 1, 1988·Archives of Neurology·J Y DelattreJ B Posner
May 1, 1984·Virology·E M MorganD W Kingsbury
Mar 1, 1997·International Journal of Radiation Oncology, Biology, Physics·L GasparR Byhardt
Mar 22, 2002·The Lancet Oncology·Isaiah J FidlerCorazon D Bucana
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Jun 21, 2003·Neuro-oncology·Paul D BrownEdward G Shaw
Dec 10, 2003·Mayo Clinic Proceedings·Robert R McWilliamsSvetomir N Markovic
Mar 18, 2004·British Journal of Clinical Pharmacology·Per EderothMargareta Hammarlund-Udenaes
May 12, 2004·Current Pharmaceutical Design·David J Begley
May 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alan SandlerChristopher A Slapak
Jun 19, 2004·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G L CeresoliE Villa
Jul 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jill S Barnholtz-SloanRaymond E Sawaya
Sep 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nancy U LinEric P Winer
Sep 24, 2004·Advanced Drug Delivery Reviews·Elizabeth C M de Lange
Sep 24, 2004·Advanced Drug Delivery Reviews·Danny D ShenKimberly K Adkison
Oct 27, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tristan S MaurerDennis O Scott
Jul 15, 2005·The New England Journal of Medicine·James H Doroshow
Sep 30, 2005·The American Journal of Pathology·Robert J WeilPatricia S Steeg
Oct 11, 2005·Journal of Neuro-oncology·Igor T Gavrilovic, Jerome B Posner
Dec 24, 2005·Nature Reviews. Neuroscience·N Joan AbbottElisabeth Hansson
Mar 18, 2006·Current Opinion in Critical Care·Lars HilleredPer Enblad
Oct 14, 2006·Cancer·Jürgen C BeckerAxel Hauschild
Dec 6, 2006·Cancer Research·Yanli ZhuangClinton F Stewart
Jan 2, 2007·Topics in Magnetic Resonance Imaging : TMRI·Marco EssigFrederik L Giesel
Apr 13, 2007·Expert Review of Anticancer Therapy·Elizabeth Fox, Susan E Bates
Jun 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elizabeth R Gerstner, Robert L Fine
Jun 27, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Markus FridénMargareta Hammarlund-Udenaes
Nov 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nienke A de VriesOlaf van Tellingen
Jan 22, 2008·The Journal of Pharmacology and Experimental Therapeutics·Xingrong LiuBill J Smith
Apr 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nancy U LinEric P Winer

❮ Previous
Next ❯

Citations

Mar 1, 2019·Journal of Neurotrauma·Samuel M PoloyacPunit Marathe
Jan 10, 2019·The Journal of Pharmacology and Experimental Therapeutics·Gautham GampaWilliam F Elmquist
Aug 16, 2019·Current Opinion in Oncology·Riccardo SoffiettiRoberta Rudà
Jun 30, 2019·Neurology·Alessia PellerinoRiccardo Soffietti
Oct 18, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Minjee KimWilliam F Elmquist
Oct 12, 2019·Nature Reviews. Cancer·Costas D ArvanitisRakesh K Jain
Sep 3, 2020·Nature Reviews. Neurology·Riccardo SoffiettiRoberta Rudà
Sep 4, 2020·British Journal of Clinical Pharmacology·Rémi LonguespéeWalter E Haefeli
Apr 30, 2021·Cellular Oncology (Dordrecht)·Bikashita Kalita, Mohane Selvaraj Coumar
Apr 18, 2021·Translational Oncology·Robin AugustineAnwarul Hasan
Aug 3, 2021·Frontiers in Oncology·Nivedita M RatnamMark R Gilbert

❮ Previous
Next ❯

Methods Mentioned

BETA
imaging techniques
surgical resection
exome sequencing
biopsies
equilibrium dialysis

Clinical Trials Mentioned

NCT02537600
NCT01378975
NCT01781026
NCT02039947
NCT02015117
NCT01703507
NCT02374242
NCT02696993
NCT01332630
NCT01933815

Related Concepts

Related Feeds

Antiparasitics

Antiparasitics are medications which are indicated for the treatment of parasitic diseases. Discover the latest research on antiparasitics here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood-Brain Barrier Transport in Neurodegeneration

The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.

Related Papers

Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology
Huile Gao
The Journal of Pharmacology and Experimental Therapeutics
Xingrong LiuBill J Smith
Current Opinion in Investigational Drugs
W Ross Tracey, Delvin R Knight
© 2022 Meta ULC. All rights reserved