Liposomal Irinotecan Accumulates in Metastatic Lesions, Crosses the Blood-Tumor Barrier (BTB), and Prolongs Survival in an Experimental Model of Brain Metastases of Triple Negative Breast Cancer

Mohammad, Afroz S.; Griffith, Jessica; Adkins, Chris E.; Shah, Neal; Sechrest, Emily; Dolan, Emma; Terrell-Hall, Tori B.; Hendriks, Bart S.; Lee, Helen; Lockman, Paul R.

doi:10.1007/s11095-017-2278-0

Cited by 56 publications

(34 citation statements)

References 44 publications

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“…Furthermore, the covalent adherence of polyethylene glycol (PEG) molecules can be used to improve the systemic circulation of drugs [ 110 ]. PEGylated liposomal formulation of irinotecan (MM-398) improved the cytotoxic effects of irinotecan in a mouse model of brain metastasis compared to irinotecan monotherapy [ 111 ]. Liposomal formulations of irinotecan are promising new cytotoxic agents that can be utilized to treat other malignancies such as metastatic breast cancer [ 105 ].…”

Section: New Irinotecan Formulationsmentioning

confidence: 99%

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Kciuk

Marciniak

Kontek

2020

IJMS

157

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Irinotecan has been used in the treatment of various malignancies for many years. Still, the knowledge regarding this drug is expanding. The pharmacogenetics of the drug is the crucial component of response to irinotecan. Furthermore, new formulations of the drug are introduced in order to better deliver the drug and avoid potentially life-threatening side effects. Here, we give a comprehensive overview on irinotecan’s molecular mode of action, metabolism, pharmacogenetics, and toxicity. Moreover, this article features clinically used combinations of the drug with other anticancer agents and introduces novel formulations of drugs (e.g., liposomal formulations, dendrimers, and nanoparticles). It also outlines crucial mechanisms of tumor cells’ resistance to the active metabolite, ethyl-10-hydroxy-camptothecin (SN-38). We are sure that the article will constitute an important source of information for both new researchers in the field of irinotecan chemotherapy and professionals or clinicians who are interested in the topic.

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Section: New Irinotecan Formulationsmentioning

confidence: 99%

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Kciuk

Marciniak

Kontek

2020

IJMS

157

View full text Add to dashboard Cite

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“…In a rat model, brain penetration of docetaxel loaded on liposomes is greatly enhanced (100%) compared to docetaxel alone [98]. In a normal model of breast cancer brain metastasis, irinotecan was compared to a liposomal formulation (nal-IRI-50): the irinotecan metabolite SN38 accumulated in the brain metastases at 7 days after intravenous injection of nal-IRI-50, while it was undetectable with irinotecan 12 h post-administration [99].…”

Section: The Use Of Nanoparticles To Cross the Bbbmentioning

confidence: 99%

How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

Angeli

Nguyễn

Janin

et al. 2019

IJMS

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The incidence of brain metastases has increased in the last 10 years. However, the survival of patients with brain metastases remains poor and challenging in daily practice in medical oncology. One of the mechanisms suggested for the persistence of a high incidence of brain metastases is the failure to cross the blood–brain barrier of most chemotherapeutic agents, including the more recent targeted therapies. Therefore, new pharmacological approaches are needed to optimize the efficacy of anticancer drug protocols. In this article, we present recent findings in molecular data on brain metastases. We then discuss published data from pharmacological studies on the crossing of the blood–brain barrier by anticancer agents. We go on to discuss future developments to facilitate drug penetration across the blood–brain barrier for the treatment of brain metastases among cancer patients, using physical methods or physiological transporters.

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“…Preclinical data using a mouse model of brain metastases demonstrated a PEGylated liposomal formulation of irinotecan (MM-398) greatly enhanced its cytotoxic effect compared to conventional irinotecan [160]. Liposomal formulations of anthracyclines, such as Doxil®, show improved efficacy and toxicity profiles in comparison to conventional formulations [161].…”

Section: Drug Delivery Systems Intended To Target Brain Metastasesmentioning

confidence: 99%

Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases

Shah

Mohammad

Saralkar

et al. 2018

Pharmacological Research

Self Cite

110

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In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2 BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM.

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Liposomal Irinotecan Accumulates in Metastatic Lesions, Crosses the Blood-Tumor Barrier (BTB), and Prolongs Survival in an Experimental Model of Brain Metastases of Triple Negative Breast Cancer

Abstract: Liposomal irinotecan accumulates in brain metastases, acts as depot for sustained release of irinotecan and SN-38, which results in prolonged survival in preclinical model of breast cancer brain metastasis.

Cited by 56 publications

References 44 publications

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases

Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases

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