ANG1005, a novel peptide-paclitaxel conjugate crosses the BBB and shows activity in patients with recurrent CNS metastasis from breast cancer, results from a phase II clinical study

Tang, Shou‐Ching; Kumthekar, Priya; Brenner, Andrew; Kesari, Santosh; Piccioni, David; Anders, CK; Carillo, J.A.; Chalasani, Pavani; Kabos, Peter; Puhalla, Shannon; García, Agustin A.; Tkaczuk, Katherine H.; Ahluwalia, Manmeet; Lakhani, Nehal; Ibrahim, Nuhad K.

doi:10.1093/annonc/mdw367.02

Cited by 18 publications

(9 citation statements)

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“…ANG1005 is a peptide-drug conjugate containing paclitaxel and covalently linked to Angiopep-2, using the LRP-1 transport system to cross the BBB. 59 This compound has shown interesting results in a phase II study in patients with metastatic breast cancer with recurrent BMs and achieved intracranial responses in 14% of the patients and 57% of the patients had stable disease 59 ( Table 1 ). Extracranial responses were also observed.…”

Section: Emerging Treatments In Bms From Breast Cancermentioning

confidence: 99%

Therapy of breast cancer brain metastases: challenges, emerging treatments and perspectives

et al. 2018

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Brain metastases are the most common central nervous system tumors in adults, and incidence of brain metastases is increasing due to both improved diagnostic techniques (e.g. magnetic resonance imaging) and increased cancer patient survival through advanced systemic treatments. Outcomes of patients remain disappointing and treatment options are limited, usually involving multimodality approaches. Brain metastases represent an unmet medical need in solid tumor care, especially in breast cancer, where brain metastases are frequent and result in impaired quality of life and death. Challenges in the management of brain metastases have been highlighted in this review. Innovative research and treatment strategies, including prevention approaches and emerging systemic treatment options for brain metastases of breast cancer, are further discussed.

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Section: Emerging Treatments In Bms From Breast Cancermentioning

confidence: 99%

Therapy of breast cancer brain metastases: challenges, emerging treatments and perspectives

et al. 2018

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“…Several molecular, biological, and physical methods have been proposed to improve transport across the BBB [ 78 ]. For example, a phase II study found that ANG1005 (a lipoprotein receptor-related protein 1-targeting peptide bound to paclitaxel) increased delivery and median survival in breast cancer patients with BMs [ 79 ].…”

Section: Brain Metastases Heterogeneity In Major Malignanciesmentioning

confidence: 99%

Molecular Profiles of Brain Metastases: A Focus on Heterogeneity

Ali

Górska

Duchnowska

et al. 2021

Cancers

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Brain metastasis is a common and devastating clinical entity. Intratumor heterogeneity in brain metastases poses a crucial challenge to precision medicine. However, advances in next-generation sequencing, new insight into the pathophysiology of driver mutations, and the creation of novel tumor models have allowed us to gain better insight into the genetic landscapes of brain metastases, their temporal evolution, and their response to various treatments. A plethora of genomic studies have identified the heterogeneous clonal landscape of tumors and, at the same time, introduced potential targets for precision medicine. As an example, we present phenotypic alterations in brain metastases originating from three malignancies with the highest brain metastasis frequency: lung cancer, breast cancer, and melanoma. We discuss the barriers to precision medicine, tumor heterogeneity, the significance of blood-based biomarkers in tracking clonal evolution, the phylogenetic relationship between primary and metastatic tumors, blood–brain barrier heterogeneity, and limitations to ongoing research.

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“…GRN1005 a peptide-drug conjugate (taxane paclitaxel and angiopep-2 (ANG=TFFYGGSRGKRNNFKTEEY)) that interacts with lipoprotein receptor-related protein 1 (LRP1) has shown excellent permeability across the BBB. Phase I and II clinical trials suggested that GRN1005 was able to cross the BBB and limit tumour growth [42,43]. Similarly, Li et al (2016) used a combination of two peptides (ANG and TAT) conjugated with paclitaxel to deliver the drug across the BBB [44].…”

Section: Novel Shuttle Peptidesmentioning

confidence: 99%

Peptide based drug delivery systems to the brain

Islam

Leach

Smith³

et al. 2020

Nano Express

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With estimated worldwide cost over $1 trillion just for dementia, diseases of the central nervous system pose a major problem to health and healthcare systems, with significant socio-economic implications for sufferers and society at large. In the last two decades, numerous strategies and technologies have been developed and adapted to achieve drug penetration into the brain, evolving alongside our understanding of the physiological barriers between the brain and surrounding tissues. The blood brain barrier (BBB) has been known as the major barrier for drug delivery to the brain. Both invasive and minimally-invasive approaches have been investigated extensively, with the minimallyinvasive approaches to drug delivery being more suitable. Peptide based brain targeting has been explored extensively in the last two decades. In this review paper, we focused on self-assembled peptides, shuttle peptides and nanoparticles drug delivery systems decorated/conjugated with peptides for brain penetration.Abbreviations

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ANG1005, a novel peptide-paclitaxel conjugate crosses the BBB and shows activity in patients with recurrent CNS metastasis from breast cancer, results from a phase II clinical study

Cited by 18 publications

References 0 publications

Therapy of breast cancer brain metastases: challenges, emerging treatments and perspectives

Therapy of breast cancer brain metastases: challenges, emerging treatments and perspectives

Molecular Profiles of Brain Metastases: A Focus on Heterogeneity

Peptide based drug delivery systems to the brain

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