Increasing Anti-Cancer Drug Efficacy with a Tumor- Penetrating Peptide

Anti-cancer drugs work by inhibiting the proliferation of oncogenic cells by a wide array of mechanisms. However, the therapeutic efficacy of these drugs can be restricted by their ability to penetrate into tumors. Limited penetration of chemotherapeutic drugs is thought to be a potential cause of resistance to cancer therapy. This phenomenon is postulated to occur due to a larger distance of cancer cells from blood vessels in comparison to normal tissue. That is, poor penetration of drugs that curb the growth of cancer cells may be due, in part, to a lack of adequate delivery from the bloodstream. A new study published in the journal Science assessed the use of a "tumor-penetrating peptide" to increase the efficacy of anti-cancer drugs.

The authors used the tumor-penetrating peptide known as iRGD. This peptide binds specifically to receptor molecules found on blood vessels that surround tumors. After binding, the peptide is then modified such that it attracts neuropilin-1, a mediator of vascular permeability. The author's hypothesis was that the administration of this peptide would increase the penetration of anti-cancer drugs when given in combination.

To test this hypothesis, the authors xenografted breast and prostate cancer cells into mice to grow solid tumors. Anticancer drugs, such as Nab-paclitaxel, doxorubicin, doxorubicin liposomes, and trastuzumab, were used to treat the tumors alone or in combination with iRDG.

No matter the case, co-administration of iRDG increased the accumulation of anticancer drug levels in established tumors in mice. Interestingly, accumulation of drug was observed in tumors alone and not in normal tissue. When not given with iRDG, the level of the anticancer drug given was relatively similar in both the tumor and normal tissue. That is, iRDG co-administration led to specific accumulation of the given drug in tumors but not in other tissues.

Consistent with this result, coadministration of iRDG also increased the efficacy of the given anticancer drug in reducing tumor weight. iRDG co-administration with doxorubicin liposimes reduced the extent of cardiotoxcicity by the drug as well, a well known adverse effect of this drug. This suggests that iRDG can not only enrich tumors with an anticancer drug, but may also aid in reducing toxicity in normal tissues.

This technology has multiple benefits for treating tumors with anti-cancer drugs. First, it enriches the drug in the tumor to increase efficacy and specificity. Secondly, it may allow for lower dosages and reduced side effects in treated patients. Lastly, it may reduce mortality by increasing the effectiveness of drug regimens against tumors that become resistant.

References:

Sugahara KN, et, al. Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science. 2010 May 21;328(5981):1031-5.