Combining synthetic, natural toxins could disarm cancer, drug-resistant bacteria

Cancer researchers from Rice University suggest that a new man-made drug that's already proven effective at killing cancer and drug-resistant bacteria could best deliver its knockout blow when used in combination with drugs made from naturally occurring toxins.

''One of the oldest tricks in fighting is the one-two punch - you distract your opponent with one attack and deliver a knockout blow with another,'' said José Onuchic of Rice's Center for Theoretical Biological Physics (CTBP). ''Combinatorial drug therapies employ that strategy at a cellular level.

Rice University scientists have proposed using a combination of drugs to fight cancer and drug-resistant bacteria. The drug cocktails would contain a synthetic drug with a "counterclockwise" twist not found in nature as well as clockwise-shaped natural toxins.

''A wealth of research in recent years has shown that both cancer and bacteria can mount sophisticated, coordinated defences against almost any drug,'' said Onuchic, Rice's Harry C. and Olga K. Wiess Professor of Physics and Astronomy, professor of chemistry, and biochemistry and cell biology. ''By combining drugs, particularly those that place stress on different parts of the cell, we expect it will be possible to knock out either cancer cells or bacteria while simultaneously inhibiting their ability to become drug-resistant.''

Onuchic and CTBP colleagues Eshel Ben-Jacob and Patricia Jennings reached their conclusions after analysing several studies on anti-microbial peptides (AMPs), corkscrew-shaped chains of amino acids that kill Gram-negative bacteria.

The CTBP team's ideas appear this week in the Proceedings of the National Academy of Sciences (PNAS) as a commentary on new findings from MD Anderson Cancer Center about a promising synthetic AMP called D-KLAKLAK-2. In its new research, MD Anderson researchers found D-KLAKLAK-2, which was already known to kill cancer cells, is also an effective drug against antibiotic-resistant Gram-negative bacteria.