2 drugs help fight kidney cancer and breast cancer
Volume 1, Issue 3, 2012
John A. Copland III, Ph.D.
Researchers at the Mayo Clinic Cancer Center in Florida have discovered a potentially powerful new approach to treating two metastatic cancers — triple-negative breast cancer and clear cell renal cell carcinoma, the most common form of kidney cancer. In the online issue of Molecular Cancer Therapeutics, they reported that two drugs, romidepsin and decitabine, work cooperatively to activate a potent tumor suppressor gene that is silenced in these two types of cancer. Once the gene — known as secreted frizzled-related protein one (sFRP1) — went to work after the drugs were used, the laboratory tumor cells stopped growing and died.
Both drugs are approved by the Food and Drug Administration to treat blood cancer and are being tested individually in numerous solid cancers in which sFRP1 is disabled. This study was the first to test the use of these drugs in metastatic cancers linked to sFRP1, and the results are encouraging, said senior investigator John A. Copland III, Ph.D., a Mayo Clinic Cancer Center molecular biologist.
"We now have the basis for a clinical trial aimed at providing effective therapy for two drug-resistant cancers and perhaps many more tumor types in the future," Dr. Copland said. In addition to breast cancer and kidney cancer, sFRP1 is disabled in other types of cancer, including colon cancer, ovarian cancer, lung cancer and liver cancer.
Dr. Copland and his colleagues earlier discovered that sFRP1 was silenced in certain cancers. This new work demonstrates that its expression can be restored by romidepsin, which is a histone deacetylase inhibitor, and decitabine, a methyltransferase inhibitor. Both are epigenetic drugs, modifying genes in a way that affects whether they are turned on or off.
"Individually, each drug did not induce any form of cell death, but together, they killed all of the different cell lines of kidney and triple-negative breast cancer that we tested in the laboratory," said lead investigator Simon J. Cooper, Ph.D., a Mayo Clinic molecular biologist who specializes in renal cancer.
The two cancers affect up to 80,000 Americans each year, and therapies to treat both, especially when the cancers are advanced, have been limited, said co-author Edith A. Perez, M.D., deputy director at large of the Mayo Clinic Cancer Center.
"But now, not only do we have a very promising lead on future therapy, but if this combination treatment works as we hope it does, we will have a biomarker to be able to test which patients might benefit the most," she said. "In other words, a biopsy test could identify patients whose tumors had lost sFRP1 function."
The approach to finding this potential new treatment strategy is novel, said Mayo Clinic Cancer Center oncologist Michael E. Menefee, M.D., also a study co-author. "This type of interdisciplinary preclinical research effort is important not only because of the value of the science, but also because the drugs are already in the clinic and that will facilitate translational efforts and hopefully confirm the preclinical findings in patients with advanced malignancies," he said.