"This is an important breakthrough," said Paul Gumerlock, associate professor of hematology & oncology at UC Davis Cancer Center and an author of the study. "It suggests a combination of drugs that block EGFR expression with drugs that block HER2 expression may have potent activity against a previously untreatable form of lung cancer."
Iressa and Tarceva are examples of EGFR blockers; Herceptin was the first HER2 blocker to reach the market. All three drugs are examples of a new generation of so-called "smart" chemotherapy agents that specifically target cancer cells.
About 3 percent of all lung cancer patients have pure BAC tumors, and about 20 percent of all non-small cell lung cancers possess some BAC features. Unlike most lung cancers, BAC occurs more frequently in women than in men, and more frequently in non smokers than in smokers. It appears to be increasing in incidence. Patients with BAC generally live longer than those with more common non-small cell lung cancers, but BAC tumors are usually too diffuse for surgery and unresponsive to existing chemotherapeutic agents.
Preliminary research from other centers and anecdotal reports from around the country have suggested a role for the EGFR blockers Iressa and Tarceva in BAC. The UC Davis study provides new evidence that combining an EGFR blocker with an HER2 blocker may be more effective than an EGFR blocker alone.
In the study, UC Davis investigators examined tissue specimens collected from BAC patients enrolled in a previous clinical trial of the drug paclitaxel. The specimen bank represents one of the largest collections of BAC tissue in the country. Wilbur Franklin, professor of pathology at the University of Colorado in Denver, participated in the study. The investigators found that although EGFR and HER2 expression varied among the tumors, BAC proliferation correlated with HER2 but not EGFR expression.
"This suggests that perhaps it's the combination of EGFR and HER2 that may explain the unusual biology of BAC," Gumerlock said. Scientists at UC Davis Cancer Center, who participated in the design of the first clinical trial of Iressa in BAC patients, now hope to launch a clinical trial of HER2- and EGFR-blocker combination therapy in the treatment of BAC.