Find in Library

Low-grade serous carcinoma represents a minority of serous carcinoma. Although they have better prognosis than high-grade serous carcinoma, they respond poorly to chemotherapy. Thus, it appears necessary to find other treatments such as targeted therapies. Since <i>RAS</i> or <i>RAF</i> mutations occur frequently in low-grade serous carcinoma and lead to constitutively activated MAPK cascade, MEK inhibition should be effective in the treatment of low-grade serous carcinoma. So, we wanted to evaluate the clinical benefit of MEK inhibitors in the management of advanced-stage low-grade serous carcinoma harboring <i>KRAS</i> or <i>NRAS</i> mutation. We report a case series of three women with advanced-stage low-grade serous carcinoma harboring <i>RAS</i> mutation who had stabilization of their disease during several months under targeted therapy combining anti-EGFR antibody and MEK inhibitor. We performed in vitro experiments, confirming the effectiveness of MEK inhibitor on the <i>KRAS</i>-mutated OVCAR-5 cell line, and the constitutively activation of MAPK cascade in <i>RAS</i>-mutated carcinoma. However, it seems that the anti-EGFR antibody does not provide any additional benefit. After whole exome analysis is carried out on the patient with the shortest response, we observed the appearance of RB1 loss-of-function mutation that could be a mechanism of resistance to MEK inhibitors in <i>RAS</i>- of <i>RAF</i>-mutated cancers. The MEK inhibitor is effective in the advanced stages of low-grade serous carcinoma harboring <i>RAS</i> mutation with acceptable tolerance. RB1 loss could be a mechanism of resistance to MEK inhibitors in <i>RAS</i>-mutated low-grade serous carcinoma.