A combination of two targeted therapies already shown to be effective in breast cancer packs an effective one-two punch against a subset of gastric cancers that have a specific genetic mutation, a study at UCLA's Jonsson Comprehensive Cancer Center has found.
The drugs Herceptin and Tykerb when given together proved to significantly inhibit tumor growth in gastric cancers that had amplified levels of HER2, a mutation that results in an aggressive form of the disease, causing the cancers to grow and spread faster. The work was done both on cell lines and in animal models with human HER2-amplified gastric cancers.
Between 18 and 27 percent of gastric cancers exhibit HER2 amplification, so the finding - if confirmed in humans - could provide a new, more effective and less toxic treatment option for tens of thousands of patients diagnosed every year worldwide with gastric cancers that carry the mutation, said Dr. Zev Wainberg, a Jonsson Cancer Center researcher and first author of the study.
"This study adds further support to the concept that if you target a specific gene in gastric cancer, a more tailored treatment approach can be considered," said Wainberg, an assistant professor of hematology/oncology. "This study also provides further proof to what we already know - that is that gastric cancer is ripe for the development of targeted therapies."
The study appears in the March 1, 2010 issue of the journal Clinical Cancer Research.
Herceptin, developed based on basic and clinical research done in Jonsson Cancer Center laboratories, has been combined with chemotherapy with great success to treat first women with HER2 amplified metastatic breast cancer and, later, women with earlier stages of disease. Tykerb was approved in 2007 for use in breast cancer. The two drugs also have been tested together in breast cancer, and the combination has recently been shown to be better than Herceptin alone in women who had previously progressed while on the single drug.
Tykerb was tested at UCLA for use in gastric cancers, first in cell lines and animal models, and was shown to be effective in cancers with HER2 amplification. A randomized Phase III clinical trial testing Tykerb with chemotherapy in HER2 amplified gastric cancer patients opened recently and is currently enrolling patients.
Herceptin also has been successfully tested in HER2 amplified gastric cancer patients, Wainberg said, and is expected to be approved for that use by the U.S. Food & Drug Administration within the next six months.
Wainberg said this is the first time that Herceptin and Tykerb have been paired to fight this subset of gastric cancers.
"In our animal models, the mice that received both Herceptin and Tykerb had their tumors shrink down to virtually nothing," Wainberg said. "This suggests that in those tumors that are dependent on HER2 for growth, this combination may be a very effective treatment. The combination of therapies was much better than either Herceptin or Tykerb alone."
The dual blockade works using two mechanisms, blocking cell signaling from inside the cell as well as on the cell's surface. Herceptin, an antibody, blocks growth signals sitting on the surface of the cancer cell, while Tykerb, a tyrosine kinase inhibitor, works from inside the cell to block the signaling that results in out of control growth of the cancer cells.