Targeted drug delivery and penetration into solid tumors

Our plain-English summary of Targeted drug delivery and penetration into solid tumors, by A. Corti, F. Pastorino, F. Curnis, et al (Medicinal Research Reviews, 2012).

The study

• Authors: A. Corti, F. Pastorino, F. Curnis, W. Arap, M. Ponzoni, R. Pasqualini
• Journal: Medicinal Research Reviews
• Published: 2012;32(5):1078-91
• Type of article: Review
• Cited by: 100 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma.

© 2011 Wiley Periodicals, Inc.

In plain English

This article is a review, not an original study. The authors described ways to get cancer drugs into solid tumors. One approach links drugs to peptides containing the Asn-Gly-Arg (NGR) motif, which home to tumor blood vessels. Another uses NGR-TNF, a peptide joined to tumor necrosis factor, which the review describes as altering drug penetration barriers. The article does not discuss asbestos. It mentions malignant pleural mesothelioma (MPM) because NGR-TNF was being tested in patients with that disease. Among the studies it summarized, a mouse study reported that NGR-targeted liposomal doxorubicin was taken up into neuroblastomas at least three times more than non-targeted liposomes after 24 hours. In a phase I trial of NGR-TNF, no patients had objective responses, and 39% had stable disease for a median of 12 weeks. In previously treated MPM patients, low-dose NGR-TNF gave disease control in about half. This lasted more than 4 months with treatment every three weeks and more than 9 months with weekly treatment. A randomized double-blind phase III trial in previously treated advanced MPM started in 2010. The authors concluded that combining the two approaches could theoretically lead to more effective therapies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: review of preclinical and clinical studies on NGR peptide-based drug delivery and NGR-TNF
• Who was studied: No study population of its own. The review covers animal tumor models and phase I and phase II clinical studies in patients with solid tumors, including malignant pleural mesothelioma.
• Main results:
  • In a mouse neuroblastoma study cited by the review, uptake of NGR-liposomal doxorubicin (TVT-DOX) into tumors was at least three times higher than that of non-targeted liposomes after 24 hours.
  • In a cited phase I trial of NGR-TNF, no objective responses were seen. 39% of patients had stable disease, with a median duration of 12 weeks.
  • In cited results in previously treated MPM patients, low-dose NGR-TNF gave disease control in about half. Control lasted more than 4 months in the every-three-weeks group and more than 9 months in the weekly group.
  • A randomized double-blind phase III study started in 2010 in previously treated patients with advanced MPM. It compares NGR-TNF plus the investigator's best choice of treatment with placebo plus that treatment.
• The authors' conclusion: The authors concluded that combining drug targeting to tumor vessels with agents that alter the vessel lining could theoretically lead to more effective cancer therapies.
• Limitations the authors state:
  • The authors state it is unknown whether repeated treatments with NGR-drug conjugates select blood-vessel lining cells with reduced CD13, the receptor NGR binds to.

Topics

Medical terms in this study, explained in our Lexicon: Necrosis, Pleural Mesothelioma.

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