Scientists Uncover Peptide to Enhance Cancer Drug Effectiveness

by Rajshri on  April 10, 2010 at 8:16 PM Cancer News
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 Scientists Uncover Peptide to Enhance Cancer Drug Effectiveness
New research has demonstrated that a peptide helps co-injected drugs to penetrate deep into tumour tissue enhancing cancer drug effectiveness.

The peptide (a chain of amino acids) called iRGD has been shown to substantially increase treatment efficacy against human breast, prostate and pancreatic cancers in mice, achieving the same therapeutic effect as a normal dose with one-third as much of the drug.

Erkki Ruoslahti, distinguished professor at Sanford-Burnham edical Research Institute, said: "Drugs generally have ifficulty penetrating tumors beyond a few cell diameters from a blood vessel.

"This leaves some tumor cells with a suboptimal dose, increasing the risk of both recurrence and drug resistance. The iRGD peptide solves this problem by activating a transport system in tumours that distributes co-injected drugs into the entire tumour and increases drug accumulation in the tumour."

Dr. Ruoslahti showed in the 1980s that a 3 amino-acid peptide motif (RGD-Arginine-Glycine-Aspartic Acid) serves as a highly selective identifier of malignant tissue, binding to unique re-ceptors in the vasculature of cancers.

The RGD peptide's ability to home to tumours has been used to design new compounds for cancer diagnosis and treatment.

The new variant of RGD (iRGD-internalizing RGD) combines the RGD motif with a tissue penetration element called CendR.

Like the earlier RGD peptides, iRGD homes to tumours, but exposure of the CendR motif when the iRGD is enzymatically cleaved activates a transport system through tumour blood vessel walls into the tumour core.

In a paper published in Cancer Cell late last year, the research team showed that coupling iRGD to anti-cancer drugs allowed them to penetrate deep into tumours, effectively increasing the activity of the drugs.

The latest study adds a new and important twist to the story: The researchers made the unanticipated discovery that anti-cancer drugs do not need to be chemically attached to the iRGD peptide for iRGD to boost their efficacy.

Simply co-administering iRGD with a drug enhances the drug's anti-cancer properties. Co-administration could be even more effective at delivering therapeutic agents inside tumours than conjugating the agents with the peptide.

This new paradigm means that iRGD has the potential to enhance the efficacy of already approved drugs without creating new chemical entities, which would complicate the path to approval for clinical use.

In addition to being effective against human breast, prostate and pancreatic cancers grown in mice, iRGD can penetrate other tumour types and could possibly be used to treat most, if not all, solid tumours.

The iRGD peptide was also shown to enhance the therapeutic effects of multiple types of anti-cancer drugs, including a small molecule drug, a monoclonal antibody and two nanoparticle drugs.

Tumours essentially resistant to a particular drug showed good responses when the drug was combined with iRGD, and tumours partially responsive to another drug were eradicated by the combination.

The research has appeared in the online edition of the journal Science.

Source: ANI

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