Nanoparticles containing a combination of a drug and an antibody for the treatment of breast cancer brain metastases

Wyatt, Emily A.; Davis, Mark E.

doi:10.1021/acs.molpharmaceut.9b01167

Cited by 12 publications

(17 citation statements)

References 34 publications

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“…Indeed, albumin nanoparticles demonstrated increased delivery of lapatinib to BrM in animal models, thereby inhibiting the growth of metastases and extending survival 61 . Combination therapies have also been attempted with nanoparticle delivery, including a chemotherapy plus anti‐HER2 antibody combination, which reduced tumor volume in an intracranial HER2+ model 62 …”

Section: Preclinical Studiesmentioning

confidence: 99%

“…Nanoparticle technology has also been explored as a method to increase BrM exposure to HER2-targeting agents.Indeed, albumin nanoparticles demonstrated increased delivery of lapatinib to BrM in animal models, thereby inhibiting the growth of metastases and extending survival 61. Combination therapies have also been attempted with nanoparticle delivery, including a chemotherapy plus anti-HER2 antibody combination, which reduced tumor volume in an intracranial HER2+ model 62. There is growing appreciation for the need of combination therapies in HER2+ BCBrM, as HER2-directed therapy alone does not appear to always be sufficient.…”

mentioning

confidence: 99%

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HER2‐positive breast cancer brain metastasis: A new and exciting landscape

Zimmer

Swearingen²,

Anders³

2020

Cancer Reports

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Background: Brain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Radiation and surgery are currently the main local treatment approaches for central nervous system (CNS) metastases. Systemic anti-HER2 therapy following a diagnosis of BrM improves outcomes. Previous preclinical data has helped elucidate HER2 brain trophism, the blood-brain/blood-tumor barrier(s), and the brain tumor microenvironment, all of which can lead to development of novel therapeutic options. Recent findings: Several anti-HER2 agents are currently available and reviewed here, some of which have recently shown promising effects in BrM patients, specifically. New strategies driven by and focusing on brain metastasis-specific genomics, immunotherapy, and preventive strategies have shown promising results and are under development. Conclusions: The field of HER2+ breast cancer, particularly for BrM, continues to evolve as new therapeutic strategies show promising results in recent clinical trials. Increasing inclusion of patients with BrM in clinical studies, and a focus on assessing their outcomes both intracranially and extracranially, is changing the landscape for patients with HER2+ CNS metastases by demonstrating the ability of newer agents to improve outcomes.

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Section: Preclinical Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

HER2‐positive breast cancer brain metastasis: A new and exciting landscape

Zimmer

Swearingen²,

Anders³

2020

Cancer Reports

View full text Add to dashboard Cite

show abstract

“…This defence system is a unique problem which prevents majority of the current therapies from succeeding. Utilising lipid-soluble cargoes such as nanoparticles which disintegrate at the target site ( 215 , 216 ), or focused ultrasound techniques e.g., pulsed ultrasound ( 217 ), can greatly improve the delivery of targeted drugs.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead

et al. 2021

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The constitutive and dysregulated expression of the transcription factor MYCN has a central role in the pathogenesis of the paediatric brain tumour medulloblastoma, with an increased expression of this oncogene correlating with a worse prognosis. Consequently, the genomic and functional alterations of MYCN represent a major therapeutic target to attenuate tumour growth in medulloblastoma. This review will provide a comprehensive synopsis of the biological role of MYCN and its family components, their interaction with distinct signalling pathways, and the implications of this network in medulloblastoma development. We will then summarise the current toolbox for targeting MYCN and highlight novel therapeutic avenues that have the potential to results in better-tailored clinical treatments.

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“…These NPs also enabled controlled drug release, as pH-responsive portions of the MAP-CPT complex are cleaved due to acidification during transcytosis, releasing CPT into the brain. The same group assessed the ability of this BBB-targeting MAP delivery system to deliver trastuzumab alone or in combination with CPT [145]. Importantly for IT, which includes ICI therapeutic antibodies, this strategy was feasible for antibody delivery and found that BBB-targeted MAP-CPTtrastuzumab combination NPs result in significantly better tumor control than either therapy alone.…”

Section: Bbb Targeting and Translocation Strategiesmentioning

confidence: 99%

Harnessing nanomedicine for enhanced immunotherapy for breast cancer brain metastases

Carney

Pandey

Kapur

et al. 2021

Drug Deliv. and Transl. Res.

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Brain metastases (BMs) are the most common type of brain tumor, and the incidence among breast cancer (BC) patients has been steadily increasing over the past two decades. Indeed, ~ 30% of all patients with metastatic BC will develop BMs, and due to few effective treatments, many will succumb to the disease within a year. Historically, patients with BMs have been largely excluded from clinical trials investigating systemic therapies including immunotherapies (ITs) due to limited brain penetration of systemically administered drugs combined with previous assumptions that BMs are poorly immunogenic. It is now understood that the central nervous system (CNS) is an immunologically distinct site and there is increasing evidence that enhancing immune responses to BCBMs will improve patient outcomes and the efficacy of current treatment regimens. Progress in IT for BCBMs, however, has been slow due to several intrinsic limitations to drug delivery within the brain, substantial safety concerns, and few known targets for BCBM IT. Emerging studies demonstrate that nanomedicine may be a powerful approach to overcome such limitations, and has the potential to greatly improve IT strategies for BMs specifically. This review summarizes the evidence for IT as an effective strategy for BCBM treatment and focuses on the nanotherapeutic strategies currently being explored for BCBMs including targeting the blood–brain/tumor barrier (BBB/BTB), tumor cells, and tumor-supporting immune cells for concentrated drug release within BCBMs, as well as use of nanoparticles (NPs) for delivering immunomodulatory agents, for inducing immunogenic cell death, or for potentiating anti-tumor T cell responses. Graphical abstract

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Nanoparticles containing a combination of a drug and an antibody for the treatment of breast cancer brain metastases

Cited by 12 publications

References 34 publications

HER2‐positive breast cancer brain metastasis: A new and exciting landscape

HER2‐positive breast cancer brain metastasis: A new and exciting landscape

Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead

Harnessing nanomedicine for enhanced immunotherapy for breast cancer brain metastases

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