Cancer Drug Effectiveness Substantially Advanced
Researchers have shown that a peptide (a chain of amino acids) called iRGD helps co-administered drugs penetrate deeply into tumor tissue. The peptide 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. In a transformative paper published in the online edition of the journal Science, Erkki Ruoslahti, M.D., Ph.D., distinguished professor at Sanford-Burnham Medical Research Institute and founding member of the UC Santa Barbara-Sanford|Burnham Center for Nanomedicine, Kazuki N. Sugahara, M.D., Ph.D., Tambet Teesalu, Ph.D., and fellow researchers at the Center for Nanomedicine and the Cancer Center of Santa Barbara, announced this significant advance in cancer therapy.
“Drugs generally have difficulty penetrating tumors beyond a few cell diameters from a blood vessel,” said Dr. Ruoslahti. “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 tumors that distributes co-injected drugs into the entire tumor and increases drug accumulation in the tumor.”
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 tumors 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 tumors, but exposure of the CendR motif when the iRGD is enzymatically cleaved activates a transport system through tumor blood vessel walls into the tumor 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 tumors, effectively increasing the activity of the drugs.
The research reported in this latest Science paper 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 tumors 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. Read more
Excessive Alcohol Consumption May Lead To Increased Cancer Risk
Researchers have detected a link between alcohol consumption, cancer and aging that starts at the cellular level with telomere shortening.
Results of this cross-sectional study were presented at the American Association for Cancer Research 101st Annual Meeting 2010, held here, April 17-21 at the Walter E. Washington Convention Center.
Telomeres are found at the region of DNA sequences at the end of a chromosome, and are important for the genetic stability of cells. As people age, telomere length shortens progressively.
Excessive use of alcohol has been linked to oxidative stress and inflammation, two mechanisms that accelerate telomere shortening. Since telomere shortening is thought to increase cancer risk, the researchers speculated that those with shorter telomeres due to heavy alcohol consumption would have an increased risk of cancer.
“Heavy alcohol users tend to look haggard, and it is commonly thought heavy drinking leads to premature aging and earlier onset of diseases of aging. In particular, heavy alcohol drinking has been associated with cancer at multiple sites,” said lead researcher Andrea Baccarelli, M.D., Ph.D. Read more