Probing Cancer Drug Resistance

New insights about cancer cell resistance to chemotherapy might follow from observations by a team of researchers at UCLA about how some cells respond to the drug cisplatin. The work, which has not yet been published, was presented last week at the American Chemical Society national meeting in Anaheim, Calif.

Using atomic force microscopy (AFM), the team, led by chemist James K. Gimzewski, probed the stiffening of ovarian cancer cells when they were treated with cisplatin. Cancer cells are usually softer than normal cells in surrounding tissue because their inner and outer architecture has been remodeled in the process of malignancy. Cisplatin treatment, in the case of ovarian cancer, appears to reverse the trend, said Shivani Sharma, one of the UCLA project scientists.

Ovarian cancer is the most lethal gynecological malignancy, Sharma said. Fifteen percent of all patients are resistant to cisplatin, the "gold standard" of treatment for the disease, she added. In addition, some patients develop resistance to the drug after chemotherapy.

Gimzewski, Sharma, and coworkers administered cisplatin to and tested the stiffness of both drug-sensitive ovarian cancer cells and drug-resistant cells using AFM. When treated with the drug, the sensitive cells exhibited a significant increase in rigidity, and the insensitive cells hardened only slightly.

"The biology of chemotherapeutic resistance is not well understood," said Mark Banaszak Holl, a biophysical chemist at the University of Michigan, Ann Arbor, who attended the talk. What the researchers have observed, he added, might help uncover whether there are structural differences in resistant cells that are responsible for the drug's ineffectiveness. In addition, further work could elucidate how the drug triggers architectural remodeling in the cells.

An understanding of the structural properties of a diseased or drug-resistant cell might enable researchers to design more effective drugs, said Igor Sokolov, a microscopy researcher at Clarkson University. When combined with other cancer-treatment screening techniques, he added, AFM could be a powerful future player.