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Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA

التفاصيل البيبلوغرافية
العنوان: Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA
المؤلفون: Bojan Losic, Leopold Garnar-Wortzel, Li Lin, Jun Liao, Peter Dottino, Mark S. Chee, Nolan Priedigkeit, Pratik Lahiri, Elena Pereira, Jian Ma, Dagny Miller, Hardik Shah, John A. Martignetti, Catalina Camacho, Olga Camacho-Vanegas, Eric E. Schadt
المصدر: Neoplasia: An International Journal for Oncology Research, Vol 16, Iss 1, Pp 97-103 (2014)
بيانات النشر: Elsevier, 2014.
سنة النشر: 2014
مصطلحات موضوعية: Cisplatin, Cancer Research, Chemotherapy, Pathology, medicine.medical_specialty, business.industry, medicine.medical_treatment, medicine.disease, Debulking, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Fusion transcript, Agarose gel electrophoresis, Cancer research, Medicine, Neoplasm, Biomarker (medicine), business, Ovarian cancer, medicine.drug
الوصف: Retrospective studies have demonstrated that nearly 50% of patients with ovarian cancer with normal cancer antigen 125 (CA125) levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here, we demonstrate that for one patient, with the first reported fibroblast growth factor receptor 2 (FGFR2) fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125, and it can also inform on a candidate therapeutic. For a 4-year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences, and multiple chemotherapeutic regimens, blood samples were longitudinally collected and stored. Whereas postsurgical CA125 levels were elevated only three times for 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and others with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhibitor treatment. Using the same methodologic approach, we demonstrate in a second patient with a different fusion that PCR and agarose gel electrophoresis can also be used to identify tumor-specific DNA in the circulation. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease.
اللغة: English
تدمد: 1522-8002
1476-5586
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8b91dca1927868265bda4431ad5faeb
http://www.sciencedirect.com/science/article/pii/S1476558614800092
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....b8b91dca1927868265bda4431ad5faeb
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15228002
14765586