Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment

Murrell, Donna H.; Zarghami, Niloufar; Jensen, Michael D.; Chambers, Ann F.; Wong, Eugene; Foster, Paula J.

doi:10.1016/j.tranon.2016.04.006

Cited by 22 publications

(33 citation statements)

References 34 publications

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“…Murrell D.H., et al (2016) did not found changes in BBB permeability at the 1st and 11th days after radiation in mice after WBRT therapeutically relevant doses to human equivalent doses. The results of clinical studies have not revealed an increase in clinical effectiveness in the concurrent use of radiation and chemotherapy [16]. The BBB permeability modification under the influence of radiation on the BM at the moment is controversial and needs further study.…”

Section: Influence Of Radiation Therapy On the Bbb Permeabilitymentioning

confidence: 99%

Management of Brain Metastases from Solid Tumors

Любота¹,

Верещако²,

Anikusko³

et al. 2018

Cancer Management and Therapy

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Brain metastases (BM) are most common intracranial tumors in adults. Recently, significant progress has been shown in diagnosing, prognosis, and treating patients with BM of various malignant tumors. The treatment decisions must be based on the disease prognosis and include radiation therapy, surgery, systemic antitumor therapy, or a combination thereof. Systemic therapy capable of preventing BM or which affects both intracranial and extracranial disease is of paramount importance in the treatment of BM patients. The purpose of this chapter is to consider important prognostic factors that can determine treatment decisions, review the role of blood-brain barrier (BBB), and systemic anticancer treatment to manage BM from solid tumors.

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Section: Influence Of Radiation Therapy On the Bbb Permeabilitymentioning

confidence: 99%

Management of Brain Metastases from Solid Tumors

Любота¹,

Верещако²,

Anikusko³

et al. 2018

Cancer Management and Therapy

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“…Smith and Lockman used quantitative imaging following injection of dyes and radiolabeled drugs (Lockman et al 2010), the laboratories of Drs. Foster and Chambers used gadolinium CE-MRI and high-resolution anatomic MRI to understand permeability of brain metastases in breast cancer models, and observed it to be heterogeneous (Murrell et al 2016; Murrell et al 2015). The laboratory of Dr. Winkler, confirms such findings of heterogeneity in permeability of brain metastases in a melanoma mouse model.…”

Section: ) Blood-brain Barrier: An Obstacle For Drug Delivery To Bramentioning

confidence: 99%

“…It is critical to realize that the successful treatment of MBM, or any brain metastases, with molecularly-targeted agents will depend on the development of novel therapeutic agents that are not only potent at the target site, but are also capable of penetrating an intact BBB and reaching the protected metastatic tumor cells that are not clinically detectable upon contrast-enhanced MR imaging (Murrell et al 2016). Several critical questions surrounding the clinical diagnoses and treatment of MBM are addressed in this perspective, and adequate drug delivery is a component of each of these critical clinical questions.…”

Section: ) Introductionmentioning

confidence: 99%

Drug delivery to melanoma brain metastases: Can current challenges lead to new opportunities?

Gampa

Vaidhyanathan

Sarkaria

et al. 2017

Pharmacological Research

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Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease. While these studies are encouraging, there remains significant room for improvement in the treatment of MBM, given the lack of durable response and the development of resistance to current therapies. Critical questions remain regarding mechanisms that lead to this lack of durable response and development of resistance, and how those mechanisms may differ in systemic sites versus brain metastases. One issue that may not be fully appreciated is that the delivery of several small molecule molecularly-targeted therapies to the brain is often restricted due to active efflux at the blood-brain barrier (BBB) interface. Inadequate local drug concentrations may be partially responsible for the development of unique patterns of resistance at metastatic sites in the brain. It is clear that there can be local, heterogeneous BBB breakdown in MBM, as exemplified by contrast-enhancement on T1-weighted MR imaging. However, it is possible that the successful treatment of MBM with small molecule targeted therapies will depend, in part, on the ability of these therapies to penetrate an intact BBB and reach the protected micro-metastases (so called “sub-clinical” disease) that escape early detection by contrast-enhanced MRI, as well as regions of tumor within MRI-detectable metastases that may have a less compromised BBB. The emergence of resistance in MBM may be related to several diverse, yet interrelated, factors including the distinct microenvironment of the brain and inadequate brain penetration of targeted therapies to specific regions of tumor. The tumor microenvironment has been ascribed to play a key role in steering the course of disease progression, by dictating changes in expression of tumor drivers and resistance-related signaling mechanisms. Therefore, a key issue to consider is how changes in drug delivery, and hence local drug concentrations within a metastatic microenvironment, will influence the development of resistance. Herein we discuss our perspective on several critical questions that focus on many aspects relevant to the treatment of melanoma brain metastases; the answers to which may lead to important advances in the treatment of this devastating disease.

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“…For example, technological advances in multiphoton laser scanning microscopy have improved our ability to survey single steps of the CNS metastatic cascade via live imaging through a chronic cranial window in vivo [29]. A modified MRI modality has been applied to evaluate the integrity of the blood-brain barrier in mouse model bearing the MDA-MB-213 breast cancer brain metastasis [30]. Intriguingly, the glial cells are activated and have upregulated translocator protein (TSPO) in response to metastasis; thus, agents targeting the upregulated translocator protein (TSPO) on activated glia have been developed for SPECT/PET imaging [31].…”

Section: New Models and Tools To Study Brain Metastasismentioning

confidence: 99%

“…Therefore, there have been extensive efforts recently aiming to understand the biology of tumor-BBB interaction and to find novel ways that facilitate drug delivery through the BBB. To this end, the permeability of blood-brain barrier is highly heterogeneous at sites of metastasis [79,80,30]. Furthermore, pericytes were shown to have significant contribution to the permeability of blood-tumor barrier in multiple experimental breast cancer brain metastasis models [81].…”

Section: New Biological Insights On Brain Metastasismentioning

confidence: 99%

Advances in decoding breast cancer brain metastasis

Zhang

2016

Cancer Metastasis Rev

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The past decade has witnessed impressive advances in cancer treatment ushered in by targeted and immunotherapies. However, with significantly prolonged survival, upon recurrence, more patients become inflicted by brain metastasis, which is mostly refractory to all currently available therapeutic regimens. Historically, brain metastasis is an understudied area in cancer research, partly due to the dearth of appropriate experimental models that closely simulate the special biological features of metastasis in the unique brain environment; and to the sophistication of techniques required to perform in-depth studies of the extremely complex and challenging brain metastasis. Yet, with increasing clinical demand for more effective treatment options, brain metastasis research has rapidly advanced in recent years. The present review spotlights the recent major progresses in basic and translational studies of brain metastasis with focuses on new animal models, novel imaging technologies, omics “big data” resources, and some new and exciting biological insights on brain metastasis.

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Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment

Cited by 22 publications

References 34 publications

Management of Brain Metastases from Solid Tumors

Management of Brain Metastases from Solid Tumors

Drug delivery to melanoma brain metastases: Can current challenges lead to new opportunities?

Advances in decoding breast cancer brain metastasis

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