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Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs.

ABSTRACT: Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions, including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, coadministration of iRGD may be a valuable way to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research.

SUBMITTER: Sugahara KN

PROVIDER: S-EPMC2881692 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs.

Sugahara Kazuki N KN Teesalu Tambet T Karmali Priya Prakash PP Kotamraju Venkata Ramana VR Agemy Lilach L Greenwald Daniel R DR Ruoslahti Erkki E

Science (New York, N.Y.) 20100408 5981

Poor penetration of anticancer drugs into tumors can be an important factor limiting their efficacy. We studied mouse tumor models to show that a previously characterized tumor-penetrating peptide, iRGD, increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing coadministered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRG ...[more]

PMID: 20378772

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Replication Study: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs.

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