History of the development of DOXIL^|^reg;

Takahara, T.; Mukai, Harumi Y.

doi:10.2745/dds.28.205

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…Doxil ® gathers in interstitial cavities of solid cancer tissues, such as ovarian cancer and breast cancer, based on the EPR effect and releases doxorubicin molecules there. At present, Doxil ® is clinically used for the treatment of ovarian cancer and breast cancer [ 41 ]. Although doxorubicin transports the membrane through passive diffusion [ 81 ], it is a substrate of MDR1 [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

Tashima

2022

Antibodies

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Innumerable people worldwide die of cancer every year, although pharmaceutical therapy has actualized many benefits in human health. For background, anti-cancer drug development is difficult due to the multifactorial pathogenesis and complicated pathology of cancers. Cancer cells excrete hydrophobic low-molecular anti-cancer drugs by overexpressed efflux transporters such as multiple drug resistance 1 (MDR1) at the apical membrane. Mutation-driven drug resistance is also developed in cancer. Moreover, the poor distribution of drug to cancer cells is a serious problem, because patients suffer from off-target side effects. Thus, highly selective and effective drug delivery into solid cancer cells across the membrane should be established. It is known that substances (10–100 nm in diameter) such as monoclonal antibodies (mAbs) (approximately 14.2 nm in diameter) or nanoparticles spontaneously gather in solid tumor stroma or parenchyma through the capillary endothelial fenestration, ranging from 200–2000 nm, in neovasculatures due to the enhanced permeability and retention (EPR) effect. Furthermore, cancer antigens, such as HER2, Nectin-4, or TROP2, highly selectively expressed on the surface of cancer cells act as a receptor for receptor-mediated endocytosis (RME) using mAbs against such antigens. Thus, antibody–drug conjugates (ADCs) are promising anti-cancer pharmaceutical agents that fulfill accurate distribution due to the EPR effect and due to antibody–antigen binding and membrane permeability owing to RME. In this review, I introduce the implementation and possibility of highly selective anti-cancer drug delivery into solid cancer cells based on the EPR effect and RME using anti-cancer antigens ADCs with payloads through suitable linkers.

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Section: Discussionmentioning

confidence: 99%

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

Tashima

2022

Antibodies

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Molecular Assemblies Composed of Phospholipids for Pharmaceutical Formulations

Kawakami

2016

Journal of the Japan Society of Colour Material

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Analysis of the Factors Influencing the Development of Hand-foot Syndrome in Patients Receiving Pegylated Liposomal Doxorubicin Therapy for Ovarian Cancer

諒

克之

武司

et al. 2016

Jpn. J. Pharm. Health Care Sci.

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Pegylated liposomal doxorubicin (PLD) is a liposomal formulation of doxorubicin hydrochloride. It was approved for the treatment of ovarian cancer aggravated after chemotherapy. The occurrence of hand-foot syndrome (HFS) associated with the administration of PLD is considered one of the major adverse side effects. The development of Grade2 ≦ HFS (Serious HFS) during the course of PLD therapy calls for dose reduction or discontinuation of subsequent PLD administration. However, the factors that influence the development of HFS are unclear in Japan. Therefore, we focused on the factors influencing the development of HFS in patients receiving PLD therapy for ovarian cancer. The study population consisted of 36 patients. Twenty patients (55.6％) developed HFS while 10 patients (27.8％) developed serious HFS. The patients who did not develop stomatitis during PLD therapy, also never developed serious HFS. In contrast, 37.0％ (10/27) of the patients who had developed stomatitis during PLD therapy were reported to have developed serious HFS (P = 0.0390). For the 10 patients with serious HFS, the median time for the occurrence of serious HFS and stomatitis after the initiation of PLD therapy was 3 cycles and 1 cycle, respectively. In conclusion, patients who developed stomatitis during the course of PLD therapy were more likely to develop serious HFS than those who did not. Additionally, stomatitis has been reported to develop prior to serious HFS. Therefore, the occurrence of stomatitis during PLD therapy can aid in the prediction of serious HFS development in future.

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History of the development of DOXIL^|^reg;

Cited by 4 publications

References 10 publications

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

Molecular Assemblies Composed of Phospholipids for Pharmaceutical Formulations

Analysis of the Factors Influencing the Development of Hand-foot Syndrome in Patients Receiving Pegylated Liposomal Doxorubicin Therapy for Ovarian Cancer

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