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Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases.
Lim, Malcolm; Puttick, Simon; Houston, Zachary H; Thurecht, Kristofer J; Kalita-de Croft, Priyakshi; Mahler, Stephen; Rose, Stephen E; Jeffree, Rosalind L; Mazzieri, Roberta; Dolcetti, Riccardo; Lakhani, Sunil R; Saunus, Jodi M.
Affiliation
  • Lim M; Faculty of Medicine, the University of Queensland, Centre for Clinical Research, Herston, Queensland 4029, Australia. m.lim@uq.edu.au.
  • Puttick S; Probing Biosystems Future Science Platform, CSIRO Health & Biosecurity, Herston, Queensland 4029, Australia. Simon.Puttick@csiro.au.
  • Houston ZH; Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland 4072, Australia. z.houston@uq.edu.au.
  • Thurecht KJ; Centre for Advanced Imaging, the University of Queensland, St Lucia, Queensland 4072, Australia. z.houston@uq.edu.au.
  • Kalita-de Croft P; ARC Centre of Excellence in Convergent BioNano Science and Technology, the University of Queensland, St Lucia, Queensland 4072, Australia. z.houston@uq.edu.au.
  • Mahler S; Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland 4072, Australia. k.thurecht@uq.edu.au.
  • Rose SE; Centre for Advanced Imaging, the University of Queensland, St Lucia, Queensland 4072, Australia. k.thurecht@uq.edu.au.
  • Jeffree RL; ARC Centre of Excellence in Convergent BioNano Science and Technology, the University of Queensland, St Lucia, Queensland 4072, Australia. k.thurecht@uq.edu.au.
  • Mazzieri R; Faculty of Medicine, the University of Queensland, Centre for Clinical Research, Herston, Queensland 4029, Australia. p.kalita@uq.edu.au.
  • Dolcetti R; Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St Lucia, Queensland 4072, Australia. s.mahler@eng.uq.edu.au.
  • Lakhani SR; ARC Training Centre for Biopharmaceutical Innovation, the University of Queensland, St Lucia, Queensland 4072, Australia. s.mahler@eng.uq.edu.au.
  • Saunus JM; Probing Biosystems Future Science Platform, CSIRO Health & Biosecurity, Herston, Queensland 4029, Australia. Stephen.Rose@csiro.au.
Int J Mol Sci ; 20(6)2019 Mar 14.
Article in En | MEDLINE | ID: mdl-30875730
Brain metastases are the most prevalent of intracranial malignancies. They are associated with a very poor prognosis and near 100% mortality. This has been the case for decades, largely because we lack effective therapeutics to augment surgery and radiotherapy. Notwithstanding improvements in the precision and efficacy of these life-prolonging treatments, with no reliable options for adjunct systemic therapy, brain recurrences are virtually inevitable. The factors limiting intracranial efficacy of existing agents are both physiological and molecular in nature. For example, heterogeneous permeability, abnormal perfusion and high interstitial pressure oppose the conventional convective delivery of circulating drugs, thus new delivery strategies are needed to achieve uniform drug uptake at therapeutic concentrations. Brain metastases are also highly adapted to their microenvironment, with complex cross-talk between the tumor, the stroma and the neural compartments driving speciation and drug resistance. New strategies must account for resistance mechanisms that are frequently engaged in this milieu, such as HER3 and other receptor tyrosine kinases that become induced and activated in the brain microenvironment. Here, we discuss molecular and physiological factors that contribute to the recalcitrance of these tumors, and review emerging therapeutic strategies, including agents targeting the PI3K axis, immunotherapies, nanomedicines and MRI-guided focused ultrasound for externally controlling drug delivery.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Drug Resistance, Neoplasm / Antineoplastic Agents Type of study: Prognostic_studies Limits: Humans Language: En Journal: Int J Mol Sci Year: 2019 Document type: Article Affiliation country: Australia Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Drug Resistance, Neoplasm / Antineoplastic Agents Type of study: Prognostic_studies Limits: Humans Language: En Journal: Int J Mol Sci Year: 2019 Document type: Article Affiliation country: Australia Country of publication: Switzerland