Association of Anti-EGFR Antibody and MEK Inhibitor in Gynecological Cancer Harboring RAS Mutation: A Case Series.
Int J Mol Sci
; 23(6)2022 Mar 19.
Article
em En
| MEDLINE
| ID: mdl-35328764
ABSTRACT
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 RAS or RAF 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 KRAS or NRAS mutation. We report a case series of three women with advanced-stage low-grade serous carcinoma harboring RAS 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 KRAS-mutated OVCAR-5 cell line, and the constitutively activation of MAPK cascade in RAS-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 RAS- of RAF-mutated cancers. The MEK inhibitor is effective in the advanced stages of low-grade serous carcinoma harboring RAS mutation with acceptable tolerance. RB1 loss could be a mechanism of resistance to MEK inhibitors in RAS-mutated low-grade serous carcinoma.
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Carcinoma
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Cistadenocarcinoma Seroso
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
França