The gist: Drugs called gamma secretase inhibitors (GSI) are being explored as a potential way to overcome resistance to endocrine therapy drugs (like tamoxifen or letrozole) for women with estrogen-receptor-positive (ER+) breast cancer. A GSI drug called MK-0752 was recently given to patients in a clinical trial. The researchers found 18 tumor genes that could be used to predict how well GSI might work for a given patient. A larger study will explore the gene “signature” and measure just how effective GSI drugs are for breast cancer patients.
“Loyola researchers and collaborators have reported promising results from a novel therapeutic approach for women with estrogen-receptor-positive breast cancer.
“The new approach, a new drug class called gamma secretase inhibitors (GSI), specifically inhibits Notch and shuts down critical genes and cancer cells responsible for tumor growth.
“Kathy Albain, MD, FACP, who led the study, will present findings Dec. 11 during the 2014 San Antonio Breast Cancer Symposium.
“Existing cancer drugs are effective in killing mature breast cancer cells. But a handful of immature breast cancer stem cells are resistant to such drugs. They survive and are responsible for tumor growth and progression. Resistance to standard therapy is a major cause of death in women with estrogen-receptor-positive breast cancer. Approximately 75 percent of breast cancers are estrogen-receptor positive…
“Researchers are planning a larger, phase II study to evaluate the efficacy of the GSI class of drugs added to endocrine therapy versus endocrine therapy alone. This study also will determine how well the 18 gene “signature” will predict who responds to therapy.
” ‘This is an exciting new strategy to overcome resistance to a very common class of drugs (tamoxifen, letrozole), so it is our hope that in the future a vast number of patients with estrogen-receptor-positive breast cancer could benefit,’ Dr. Albain said.”