PEG conjugates in clinical development or use as anticancer agents: An overview

Pasut, Gianfranco; Veronese, Francesco M.

doi:10.1016/j.addr.2009.02.010

Cited by 432 publications

(302 citation statements)

References 80 publications

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“…From these approvals, twenty years ago, numerous clinical trials of polymer-proteins conjugates have been or are being performed. Those include enzymes (arginase [104,105], arginine deiminase [104,106,107], glutaminase [108,109]) and biological response modifiers (interleukin 2 [110][111][112], interferonalpha [113][114][115][116][117][118][119], antibody fragment angiogenesis inhibitor [120,121]) bound to PEG [93,[122][123][124][125], but to the best of our knowledge there are no new FDA approvals for cancer treatment [126][127][128].…”

Section: Polymer Therapeuticsmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,460

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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Section: Polymer Therapeuticsmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,460

754

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“…47 Clinical trials of several derivatives of PEG coupled to anticancer drugs are already under way or have been completed. 43 Pegamotecan (Enzon Pharmaceuticals, Inc.)…”

Section: Peg-gemcitabinementioning

confidence: 99%

Gemcitabine versus Modified Gemcitabine: A Review of Several Promising Chemical Modifications

2012

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Gemcitabine, an anticancer agent which acts against a wide range of solid tumors, is known to be rapidly deaminated in blood to the inactive metabolite 2',2'-difluorodeoxyuridine and to be rapidly excreted by the urine. Moreover, many cancers develop resistance against this drug, such as loss of transporters and kinases responsible for the first phosphorylation step. To increase its therapeutic levels, gemcitabine is administered at high dose (1000mg/m²) causing sides effects (neutropenia, nausea…).To improve its metabolic stability, its cytotoxic activity and to

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“…When covalently conjugated to a pharmaceutically active compound, long PEG chains—typically 20–40 kDa—with their expanded radius of gyration slow down renal filtration through the glomerular pores and, thus, can extend plasma half‐life by up to one order of magnitude 7. However, despite a successful history with more than 10 approved PEGylated protein/peptide drugs to date, there is an increasing awareness of drawbacks associated with PEGylation such as the high cost of clinical grade activated PEG derivatives, the extra effort for chemical coupling and, notably, the accumulation of PEG in organs and tissues upon prolonged administration at higher doses 8…”

Section: Introductionmentioning

confidence: 99%

The polypeptide biophysics of proline/alanine‐rich sequences (PAS): Recombinant biopolymers with PEG‐like properties

Breibeck

Skerra

2017

Biopolymers

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PAS polypeptides comprise long repetitive sequences of the small L‐amino acids proline, alanine and/or serine that were developed to expand the hydrodynamic volume of conjugated pharmaceuticals and prolong their plasma half‐life by retarding kidney filtration. Here, we have characterized the polymer properties both of the free polypeptides and in fusion with the biopharmaceutical IL‐1Ra. Data from size exclusion chromatography, dynamic light scattering, circular dichroism spectroscopy and quantification of hydrodynamic and polar properties demonstrate that the biosynthetic PAS polypeptides exhibit random coil behavior in aqueous solution astonishingly similar to the chemical polymer poly‐ethylene glycol (PEG). The solvent‐exposed PAS peptide groups, in the absence of secondary structure, account for strong hydrophilicity, with negligible contribution by the Ser side chains. Notably, PAS polypeptides exceed PEG of comparable molecular mass in hydrophilicity and hydrodynamic volume while exhibiting lower viscosity. Their uniform monodisperse composition as genetically encoded polymers and their biological nature, offering biodegradability, render PAS polypeptides a promising PEG mimetic for biopharmaceutical applications.

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PEG conjugates in clinical development or use as anticancer agents: An overview

Cited by 432 publications

References 80 publications

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Gemcitabine versus Modified Gemcitabine: A Review of Several Promising Chemical Modifications

The polypeptide biophysics of proline/alanine‐rich sequences (PAS): Recombinant biopolymers with PEG‐like properties

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