Polymer-drug conjugates: Recent development in clinical oncology

Li, Chun; Wallace, Sidney

doi:10.1016/j.addr.2007.11.009

Cited by 395 publications

(243 citation statements)

References 60 publications

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“…Opaxio, in comparison with its conventional paclitaxel-based treatment, showed some safety-related advantages such as alopecia was rare, nausea and vomiting were uncommon and hypersensitivity reactions were rarely observed. A significant survival benefit has also been observed for women receiving Opaxio vs. paclitaxel [7]. These promising results have provided the confidence that PDCs can give therapeutic benefits in the field of oncology.…”

Section: Magnitude Of the Epr Effect In Different Tumour Typesmentioning

confidence: 87%

“…Clinical trials have shown evidence of tumour responses to PDC to various degrees, and some conjugates (e.g., poly-L-glutamic acid (PGA)-paclitaxel) have progressed to Phase III trials [5,6]. In spite of several advantages of PDCs over the relevant parent drugs, such as a more favourable toxicity profile, superior quality of life and a significant survival rate [7], to date, no such conjugate has entered the market place, which suggests that system design and/or patient selection are still suboptimal.…”

Section: Introductionmentioning

confidence: 99%

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Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

et al. 2014

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Abstract:Polymer-drug conjugates have demonstrated clinical potential in the context of anticancer therapy. However, such promising results have, to date, failed to translate into a marketed product. Polymer-drug conjugates rely on two factors for activity: (i) the presence of a defective vasculature, for passive accumulation of this technology into the tumour tissue (enhanced permeability and retention (EPR) effect) and (ii) the presence of a specific trigger at the tumour site, for selective drug release (e.g., the enzyme cathepsin B). Here, we retrospectively analyse literature data to investigate which tumour types have proved more responsive to polymer-drug conjugates and to determine correlations between the magnitude of the EPR effect and/or expression of cathepsin B. Lung, breast and ovarian cancers showed the highest response rate (30%, 47% and 41%, respectively for cathepsin-activated conjugates and 31%, 43%, 40%, across all conjugates). An analysis of literature data on cathepsin content in various tumour types showed that these tumour types had high cathepsin content (up to 3835 ng/mg for lung cancer), although marked heterogeneity was observed across different studies. In addition, these tumour types were also reported as having a high EPR effect. Our results suggest that a pre-screening of patient population could bring a more marked clinical benefit.

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Section: Magnitude Of the Epr Effect In Different Tumour Typesmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

et al. 2014

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“…Recently, it has been designated as an orphan drug in combination with radiotherapy for the treatment of glioblastoma multiforme (GBM) [86]. Polyglutamates are highly biocompatible, biodegradable and multifunctional polymers, which have been successfully used as building blocks in polymer-drug conjugates and polymeric micelles for various medical applications [4,14,25,87]. In the body, such degradability is triggered by cysteine proteases (particularly cathepsin B), which play a key role in the lysosomal degradation of this polymer [88].…”

Section: Drug Deliverymentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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“…The most commonly used materials include PEG, ploy(lactic-co-glycolic) acid (PLGA), polylactic acid (PLA), and polycaprolactone (PCL). 6,7 Some polymer-based therapeutics, such as Zinostatin Stimalmer, Oncaspar PEG-L-asparaginase, and Neulasta PEG-GCSF, have been clinically approved for cancer treatment, while more formulations are undergoing clinical investigations. 7 Although these clinically approved nano-based treatments exhibit promising results with reduced hazard potential, they have some drawbacks.…”

mentioning

confidence: 99%

Facilitating Translational Nanomedicine via Predictive Safety Assessment

et al. 2017

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Extensive research on engineered nanomaterials (ENMs) has led to the development of numerous nano-based formulations for theranostic purposes. Although some nano-based drug delivery systems already exist on the market, growing numbers of newly designed ENMs exhibit improved physicochemical properties and are being assessed in preclinical stages. While these ENMs are designed to improve the efficacy of current nanobased therapeutic or imaging systems, it is necessary to thoroughly determine their safety profiles for successful clinical applications. As such, our aim in this mini-review is to discuss the current knowledge on predictive safety and structure-activity relationship (SAR) analysis of major ENMs at the developing stage, as well as the necessity of additional long-term toxicological analysis that would help to facilitate their transition into clinical practices. We focus on how the interaction of these nanomaterials with cells would trigger signaling pathways as molecular initiating events that lead to adverse outcomes. These mechanistic understandings would help to design safer ENMs with improved therapeutic efficacy in clinical settings.During the past decades, engineered nanomaterials (ENMs) have been widely used in biomedical applications, such as nanomedicine, bioimaging, and tissue engineering, because of their unique biophysicochemical properties.1,2 With regard to nanomedicine applications, ENMs could be formulated as drug carriers that deliver the therapeutic reagents within the human body and increase their bioavailability and blood circulation half-life.2 Moreover, these nanocarriers could be functionalized to deliver the drug specifically to the desired target tissues (e.g., tumors) and release the payload sustainably over long periods, thereby eliminating the necessity of multiple drug administration and reducing its cytotoxic side effects toward healthy cells.2 In addition to their implementation in drug delivery, ENMs could be used for diagnostic and imaging purposes that would help to monitor the disease and administer the treatment more accurately. 2Past research in nanomedicine has led to the design of various nanomaterial-based therapeutic and diagnostic systems that are being investigated in experimental stages (e.g., in vitro and in vivo) and clinical trials or are commercially available to the corresponding patients (Table 1). Most commercialized nanomaterial-based therapeutic reagents use lipids, proteins, and polymers that could self-assemble and biodegrade with few side effects.3 Because of high biocompatibility of lipids, several commercial liposome-drug formulations have been developed, mostly relying on polyethylene glycol (PEG)-conjugated lipids, such as DOXIL, AmBisome, Epaxal, and Inflexal V, and are under clinical trials focusing on various types of disease treatments. 4,5 Polymer-based nanoparticles (NPs) also present low toxicity, but their surface functionalization may affect their safety. The most commonly used materials include PEG, ploy(lactic-co-glycolic) acid (PLGA...

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Polymer-drug conjugates: Recent development in clinical oncology

Cited by 395 publications

References 60 publications

Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

Peptide-Based Polymer Therapeutics

Facilitating Translational Nanomedicine via Predictive Safety Assessment

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