September 12, 2011

Outsmarting a Cancer Drug

(Ivanhoe Newswire) -- Scientists have found a new way to heighten or restore the potency of a widely-used cancer drug.

The drug cetuximab is an antibody that interferes with cancer cell growth by blocking a structure known as the epidermal growth factor receptor (EGFR). The drug is often effective for patients with colorectal cancer and squamous cell cancer of the head and neck, but the benefits typically do no last longer than one year. Some patients do not benefit from the drug at all.

Investigators discovered that in some cetuximab-resistant cancer cells, a protein known as ERBB2 was actively sending “grow” signals, which was circumventing the “stop growing” signals triggered by cetuximab. ERBB2´s activity resulted from an oversupply of the protein´s parent gene or a related protein when prompted by high levels of the protein heregulin.

"ERBB2 activates a critical signaling pathway that is not normally blocked by cetuximab, and in this way, subverts cetuximab's function," Pasi Janne, M.D., Ph.D., of Dana-Farber, the study's co-senior author with Kazuhiko Nakagawa, M.D., Ph.D., of Kinki University, was quoted as saying. "Because ERBB2 isn't affected by cetuximab, this is an easy way for cancers to become resistant to the drug."

These new findings suggest that combining cetuximab with ERBB2-inhibiting drugs may be an effective therapy for cancers that become resistant to cetuximab.

"We hope the findings of our study will inspire the development of clinical trials aimed at overcoming cetuximab resistance," Kimio Yonesaka, M.D., Ph.D., formerly of Dana-Farber and now at Kinki University School of Medicine, in Osaka, Japan, was quoted as saying.

"We've identified biomarkers that can be used to select cetuximab-resistant patients who may benefit from a combination of cetuximab and ERBB2 inhibitors."

SOURCE: Science Translational Medicine, September, 2011