Genotype-matched treatment for patients with advanced type I epithelial ovarian cancer (EOC)
| Autor: | Marcus O. Butler, Tracy Stockley, Philippe L. Bedard, Suzanne Kamel-Reid, Neesha C. Dhani, Stephanie Lheureux, Tong Zhang, Anna Spreafico, Lillian L. Siu, Amit M. Oza, Helen Mackay, Celeste Yu, Stephen Welch, Blaise Clarke, Patricia Shaw, Michelle K. Wilson |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine Oncology Neuroblastoma RAS viral oncogene homolog medicine.medical_specialty Pathology Genotype endocrine system diseases Combination therapy Carcinoma Ovarian Epithelial medicine.disease_cause Article GTP Phosphohydrolases Proto-Oncogene Proteins p21(ras) 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans PTEN Neoplasms Glandular and Epithelial Prospective Studies Aged Mitogen-Activated Protein Kinase Kinases Ovarian Neoplasms biology business.industry MEK inhibitor Membrane Proteins Obstetrics and Gynecology Middle Aged Clinical trial Serous fluid Genes ras 030104 developmental biology CA-125 Antigen 030220 oncology & carcinogenesis Mutation biology.protein Female KRAS business |
| Zdroj: | Gynecologic Oncology. 144:250-255 |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2016.12.002 |
| Popis: | Background Genomic alterations that activate the MAPK signaling pathway frequently occur in Type I Epithelial Ovarian Cancers (EOCs). We evaluated therapeutic response outcomes in patients with type I EOC treated with genotype-matched therapy on clinical trials enrolled in a prospective molecular profiling program. Material and methods Formalin fixed paraffin embedded tumor tissues were prospectively screened for genomic alterations using MALDI-ToF mass-spectrometry platform or targeted sequencing using the Illumina MiSeq TruSeq Amplicon Cancer Panel. Treatment outcomes on genotype-matched trials were retrospectively reviewed using RECIST version 1.1 and Gynecological Cancer Intergroup CA125 related-response criteria Results 55 patients with type I EOC underwent molecular profiling, 41 (75%) low grade serous (LGS), 9 (16%) clear cell (CC), and 5 (9%) mucinous (MC) histologies. Thirty-five patients (64%) were found to have ≥1 somatic mutations: 23 KRAS , 6 NRAS , 5 PIK3CA , 2 PTEN , 1 BRAF , 1 AKT , 1 TP53 , and 1 CTNNB1 . Fifteen patients were subsequently enrolled in genotype-matched phase I or II trials, including 14 patients with KRAS / NRAS mutations treated with MEK inhibitor targeted combinations. Among 14 RECIST evaluable patients, there were 7 partial responses (PR), 7 stable disease (SD) and 1 disease progression (PD). CA125 responses were observed in 10/10 evaluable KRAS / NRAS mutant patients treated with MEK inhibitor combinations Conclusions Genotyping and targeted sequencing of Type I EOCs frequently identifies actionable mutations. Matched treatment with MEK-based combination therapy in KRAS and/or NRAS mutant type I EOC patients is an active therapeutic strategy. |
| Databáze: | OpenAIRE |
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