scholarly journals Factors Influencing the Central Nervous System Distribution of a Novel Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GSK2126458: Implications for Overcoming Resistance with Combination Therapy for Melanoma Brain Metastases

2015 ◽  
Vol 356 (2) ◽  
pp. 251-259 ◽  
Author(s):  
S. Vaidhyanathan ◽  
B. Wilken-Resman ◽  
D. J. Ma ◽  
K. E. Parrish ◽  
R. K. Mittapalli ◽  
...  
2014 ◽  
Vol 33 (04) ◽  
pp. 347-351
Author(s):  
Pedro Tadao Hamamoto Filho ◽  
Vitor César Machado ◽  
Flávio Ramalho Romero ◽  
Luis Gustavo Ducati ◽  
Marco Antônio Zanini ◽  
...  

AbstractBrain metastases are the most common tumors within the central nervous system. Recent advances on diagnosis and treatment modalities have allowed for longer survival. In this paper we review the indication of each modality of treatment: surgery, whole brain radiotherapy and stereotactic radiosurgery, as also recent advances on the knowledge of brain metastases biology that may improve the use of medical treatment and chemotherapy.


2013 ◽  
Vol 59 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Robert R Langley ◽  
Isaiah J Fidler

BACKGROUND It is estimated that at least 200 000 cases of brain metastases occur each year in the US, which is 10 times the number of patients diagnosed with primary brain tumors. Brain metastasis is associated with poor prognosis, neurological deterioration, diminished quality of life, and extremely short survival. Favorable interactions between tumor cells and cerebral microvascular endothelial cells encourage tumor growth in the central nervous system, while tumor cell interactions with astrocytes protect brain metastases from the cytotoxic effects of chemotherapy. CONTENT We review the pathogenesis of brain metastasis and emphasize the contributions of microvascular endothelial cells and astrocytes to disease progression and therapeutic resistance. Animal models used to study brain metastasis are also discussed. SUMMARY Brain metastasis has many unmet clinical needs. There are few clinically relevant tumor models and no targeted therapies specific for brain metastases, and the mean survival for untreated patients is 5 weeks. Improved clinical outcomes are dependent on an enhanced understanding of the metastasis-initiating population of cells and the identification of microenvironmental factors that encourage disease progression in the central nervous system.


2014 ◽  
Vol 42 (8) ◽  
pp. 1292-1300 ◽  
Author(s):  
Shruthi Vaidhyanathan ◽  
Rajendar K. Mittapalli ◽  
Jann N. Sarkaria ◽  
William F. Elmquist

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v121-v132
Author(s):  
Ethan S Srinivasan ◽  
Krutika Deshpande ◽  
Josh Neman ◽  
Frank Winkler ◽  
Mustafa Khasraw

Abstract Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood–brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.


Author(s):  
Priscilla Brastianos ◽  
Michael A. Davies ◽  
Kim Margolin ◽  
Helena A. Yu

Metastases to the central nervous system (CNS) are associated with considerable morbidity and mortality in patients with cancer. Historically, very few systemic therapies have shown efficacy in this patient population. Emerging data are now demonstrating that whole-brain radiation therapy, previously considered the mainstay of treatment of brain metastases, is associated with high rates of neurotoxicity. In this new era of targeted therapy and immunotherapy, clinical outcomes are improving, and patients are living longer. Despite these improvements, there is an urgent need to design central nervous system–penetrant compounds that target the genetic mutations enriched in brain metastases and to bring these to clinical trials.


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