Jennifer Cochran, associate professor of bioengineering, has led development of a new way to target cancer cells without damaging healthy cells. Cochran and her coauthors’ research on “guided chemotherapy missiles” appeared in June issues of Molecular Cancer Therapeutics and Angewandte Chemie.
“Chemotherapy is extremely toxic since it indiscriminately kills healthy cells in addition to tumor cells,” Cochran said. “And for that reason we and others are motivated to develop ways to more selectively target chemotherapy to tumors to make it safer and more effective.”The idea is to use an engineered protein that links to molecular antennae on the surface of a cancer cell. These antennae can differentiate healthy tissue from tumor tissue and become a conduit to directly deliver chemotherapy into the tumor cells.
Chemotherapy’s toxic nature gives it many limitations; figuring out the right dosage without harming healthy tissue can be quite challenging. The engineered protein could potentially decrease these limitations with more potent chemotherapy directly administered to the tumor. The goal is increased safety for the patient.
Cochran and her team’s research on the chemotherapy missiles built on their previous work creating a tumor-targeting protein that functioned as a “molecular flashlight” to image tumors. The engineered protein used a knot-like protein called knottin that has the capacity to detect cancer cells.
“Once we saw the tumors lighting up in these experiments, it inspired us to use the same engineered protein as a vehicle to deliver drugs to tumors,” Cochran said.
Academic and industrial work has used a similar approach with large proteins called antibodies. But smaller engineered proteins such as knottin penetrate the tumor wall more easily. Tumors are dense, so smaller proteins are better at wiggling inside them.
Cochran has always had a passion for the proteins fundamental to her chemotherapy missiles. She started studying proteins with basic science and then moved on to manipulating them through design and engineering methods. Her protein fascination — along with a desire to cure cancer and help save lives — drove her latest work.
According to Cochran, the new approach is promising so far. Although the technology has been successfully tested in animals and cells in a dish, it is not ready for human use yet.
“We need to continue to test in models for therapeutic efficiency and potency before getting it to patients,” Cochran explained. “More trials need to take place, and manufacturing is a big part of the picture as well. It will cost a lot and take a lot more time, but getting it to the public is our ultimate goal.”
– published on the Stanford Daily