Studies have found that an effective combination of drugs can fight vine melanoma

grape membrane melanoma is a very invasive melanoma that affects the eyes. It is a rare disease that affects about 2,500 people in the United States each year. However, nearly half of patients with vine melanoma develop metastasis diseases that are transferred to other parts of the body, mainly the liver. The prognosis for patients with metastasis statin melanoma is very poor, with an average survival of only 17 to 20 months. Donald A. Adam Melanoma, a researcher at Moffitt Cancer Center, and the Center of Excellence for Skin Cancer are working to change that. They have identified a new combination of drugs that can effectively fight metastasis of vine melanoma cells in preclinical studies. Their findings were published in the journal Clinical Cancer Research.
MAPK protein signaling pathways are usually dissonant in skin melanoma and grape membrane melanoma. Drugs targeting proteins called MEK, which are involved in mapK signaling pathways, significantly improve the prognosis of patients with melanoma. However, a recent Phase 3 clinical trial of grape membrane melanoma found that patients treated with MEK inhibitors plus chemotherapy had a lower survival rate than those treated with chemotherapy alone.
Many patients with vine melanoma will soon develop resistance to MEK inhibitors. Moffitt's researchers, in collaboration with scientists at the UF Health Cancer Center and the Sylvester Comprehensive Cancer Center, hope to determine how this resistance develops and identify other drugs that can be used in combination with MEK inhibitors to target staphylococcal melanoma cells for destruction.
The lab team experimented with grape membrane melanoma cell lines and found that MEK inhibitors prevented them from growing; However, this inhibition is short-lived, and eventually the cell line develops resistance and continues to grow. The researchers used proteomic analysis to determine which signaling path paths were activated during MEK inhibitor resistance.
“ We identified a number of hypothetical escape pathways that were raised after MEK suppression, including pi3K/AKT pathways, ROR1/2, and IGF-1R signaling," explains Dr. Keiran Smalley, Director of Donald A at Moffitt's, explaining that Adam Melanoma and the Center of Excellence for Skin Cancer. They also found that signaling through THEP proteins helped MEK inhibitor resistance.
Since there are no drugs known to target both AKT and YAP signaling, the researchers screened 289 compounds to identify drugs that could limit MEK's ability to suppress escape. The drug type that has the greatest impact on four different grape membrane melanoma cell line is histone deacetylase (HDAC) inhibitor. HDAC regulates the expression levels of many genes involved in cancer development, and several HDAC inhibitors are currently approved for the treatment of different types of cancer. The researchers found that panobinostat was most effective in preventing the development of YAP and AKT resistance and in enhancing the role of MEK inhibitors in the cell lineage of staphylococcus melanoma. In addition, the combination therapy with panobinostat and the MEK inhibitor traminib was more effective in reducing the growth of staphylococcus melanoma tumors in mice than using any of the drugs alone.
They hope the preclinical results will lead to clinical trials in patients with vine melanoma. "We found that clinically approved pan-HDAC inhibitors effectively limited both YAP and AKT signals in vine melanoma cells, suggesting that this may be a good candidate for future clinical development," Smalley explained.
The study was funded by the Bankhead-Coley project in Florida. (Compiled by this web)