Despite the amazing diagnostic technologies, pharmaceuticals, and procedures of modern medecine, cancer still takes the lives of more than half a million people in the US every year. Characterized by the unmediated reproduction and metastasis of tumorous cells, the various forms of the disease have proved difficult to slow and often nearly impossible to cure. Treating cancer usually requires rigorous chemotherapy or invasive surgery, each involving painful side-affects and long recovery periods.
Chemotherapy, while effective, indiscriminately attacks cells that divide quickly. Thus, the fast-dividing cells lining the mouth and intestine as well as the cells that cause hair to grow are also affected, causing an array of side affects. Scientists have been searching for a new way to fight cancer that would only target cancer cells while letting healthy cells function unhindered. A team at University of California, Irvine may have found that method in protein P53, mutated forms of which are implicated in “nearly 40 percent of diagnosed cases of cancer.”
P53 is responsible for repairing damaged DNA and causing apoptosis, or programmed cell death, in cells that are damaged beyond repair. In a mutated form, P53 does not function properly, allowing cancerous cells that would normally be destroyed to proliferate. A therapy that reactivated mutated proteins could potentially surpress tumors without causing the nasty side affects of current drugs. Also, since P53 is present in so many cancer cases, a single treatment could be used against many different forms of the affliction. However, since P53 proteins “undulate constantly, much like a seaweed bed in the ocean,” sites where medicinal compounds could bind are difficult to locate.
The UCI team had to reach across disciplinal boundaries, enlisting computer scientists, molecular biologist and others to find a usable binding site. With the help of molecular dynamics, the group constructed a simulation of P53’s movements, eventually locating a transient site that could bind with stictic acid, one of forty-five small molecules they tried. Unfortunately, stictic acid is not a viable compound for pharmaceuticals, but the scientists at UCI think that other small molecules with similar characteristics will likely have similar effects and make effective treatments.