초록 ▼

○연구개발목표
췌장암 환자의 치료반응 및 예후예측 관련 임상-유전체 지표 연구
환자 유래 이종이식 모델과 종양구 배양을 기반으로 한 치료 반응 및 예후예측 반응인자 발굴
혈중순환 종양유래 DNA를 이용한 치료반응 모니터링 마커발굴

○연구개발성과
⦁정량적 성과
- SCI급 논문 총 6편 게재
- 해외 학회 포스터 발표 3회(EMBO, AACR, ESMO)
- 국내 학회 구연발표 3회, 국내 학회 포스터 발표 1회
⦁정성적 성과
- 치료 전 생검조직과 항암요법후의 수술조직이

○연구개발목표
췌장암 환자의 치료반응 및 예후예측 관련 임상-유전체 지표 연구
환자 유래 이종이식 모델과 종양구 배양을 기반으로 한 치료 반응 및 예후예측 반응인자 발굴
혈중순환 종양유래 DNA를 이용한 치료반응 모니터링 마커발굴

○연구개발성과
⦁정량적 성과
- SCI급 논문 총 6편 게재
- 해외 학회 포스터 발표 3회(EMBO, AACR, ESMO)
- 국내 학회 구연발표 3회, 국내 학회 포스터 발표 1회
⦁정성적 성과
- 치료 전 생검조직과 항암요법후의 수술조직이 match된 검체의 Comprehensive cancer panel을 이용한 유전체 분석 및 유전자 변이정보 분석 완료
- 췌장암의 환자맞춤형치료전력 혹은 정밀의학 적용을 위한 PDX 모델과 종양구 배양 확보 및 전임상 모델을 통한 항암제 반응 평가 기준 마련
- 혈중순환 종양유래 DNA를 이용한 비침습적 치료반응 평가 모니터링 시스템 구축 및 췌장암 환자의 치료반응성 모니터링을 위한 혈액 내 cell-free DNA의 적용 가능성 검증

(출처 : 요약 1p)

Abstract ▼

Purpose&Contents
< Purpose >
- Study of predictive marker for chemosensitivity in pancreatic cancer based on prognostic/predictive clinical indicators and personal genome bio-informatics
- Collect clinical data and secure samples obtained from pre-and post- concurrent chemoradiotherapy in r

Purpose&Contents
< Purpose >
- Study of predictive marker for chemosensitivity in pancreatic cancer based on prognostic/predictive clinical indicators and personal genome bio-informatics
- Collect clinical data and secure samples obtained from pre-and post- concurrent chemoradiotherapy in resectable pancreatic cancer
- Protocol for patient-derived xenograft model and spheroid culture from pancreatic cancer
- Development of predictive marker for chemotherapy response and genome analysis informatics
- Development of prognostic/predictive biomarkers based on patient-derived xenograft (PDX) model and spheroid culture for advanced pancreatic cancer

< Contents >
- Extraction of DNA and RNA from patient with resectable pancreatic cancer treated with using Gemcitabine and concurrent chmoradiotherapy screened by first section
- Analysis of gene expression data and whole exome sequensing data before and after concurrent chemoradiotherapy
- Analysis of the genome sequence and linkage analysis clinical data and development of genetic marker with chemotherapy response
- Developing patient-derived preclinical models repository to develop predictieve markers and suggest the response evaluation criteria in the PDX models and spheroid culture models.
- Protocol for patient-derived xenograft model and spheroid culture from pancreatic cancer

Results
< Quantitative Outcome >
Number of SCI papers : 6/3(Achievement/Target), 100(Accomplishment)
IF sum : 25.23/10(Achievement/Target), 100(Accomplishment)
Other achievements
1. SCI paper 6
- Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial. Pancreatology.2016
- Cytidine Deaminase as a Molecular Predictor of Gemcitabine Response in Patients with Biliary Tract Cancer. Oncology.2015
- DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study. Oncotarget. 2017
- Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study. Cancer Research and Treatment.2017
- Temporal Improvement in Survival of Patients with Hepatocellular Carcinoma in a Hepatitis B Virus-Endemic Population. Journal of Gastroenterology and Hepatology.2017
- Prognostic implications of multiplex detection of KRAS mutations in cell-free DNA from patients with pancreatic ductal adenocarcinoma. Clinical Chemistry.2018

2. International association
- 2016 EMBO (European Molecular Biology Organization) poster presentation (Development of Patient Derived Orthotopic Xenograft (PDOX) Model from Non-Surgical Tumor Tissue of Pancreatic Cancer)
- 2016 AACR (American Association for Cancer Research), poster presentation (KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer)
- 2017 ESMO (European Society for Medical Oncology) poster presentation

3. Domestic association
- 2016 Korean Pancreatobiliary Association, oral presentation (Rapid and Stable Patient Derived Orthotopic Xenograft (PDOX) Model using Needle Biopsy of Pancreatic Cancer)
- 2016 Korean Cancer Association, oral presentation (Prognostic impact of KRAS mutation in plasma cell-free DNA in patients with pancreatic cancer)
- 2016 Korean Pancreatobiliary Association (IASGO), oral presentation (KRAS mutation in Circulating DNA of Pancreatic Cancer Patients)
- 2017 Asia Pacific Cancer Conference (APCC), poster presentation (Feasibility test of KRAS mutation in urine cell-free DNA in pancreatic cancer patients)

< Qualitative Outcome >
- Gathering clinical data on patient with pancreatic cancer and securing the FFPE sample
- Secure the samples from eight patients with pair samples obtained from biopsy tissue of pre-treatment and surgery tissue of post-treatment
- Completion of data analysis on 29 (twenty-nine) FFPE samples after performing genome analysis with comprehensive cancer panel and completion of data analysis on 409 genetic mutation information
- We established the protocol for patient-derived xenograft model and spheroid culture in pancreatic cancer
- Excess tissues from 50 pancreatic carcinomas were implanted in immunocompromised mice at the National Cancer Center after approval from the Institutional Review Board.
- We conducted an orthotopic implantation of the patient’s tumor and observed that, in contrast to the subcutaneously implanted tumor, the orthotopic model was associated with high probability for successful engraftment and shorter interval time for tumor engraftment.
- We optimized the approach to generate speroid culture models from patient-derived xenograft model. Our culture conditions showed the ability to passage and survival of tissue culture cells following the frozen storage.
- Using the blood samples collected sequentially during the chemotherapy of pancreatic cancer patients, it is possible to detect the tumor-induced gene mutation in the circulating DNA and establish the possibility of monitoring the therapeutic reactivity and establishing the prognosis prediction system
- Detection of pancreatic cancer-specific oncogene mutations identified.
- Evaluation of correlation between DNA quantity and clinical features of DNA from circulating tumor
- Comparison with existing tumor markers

Expected Contribution
- molecular characterization of patient-derived patient-derived xenograft model and spheroid culture

- Criteria for chemotherapy response in patient-derived patient-derived xenograft models and spheroid culture models

- Development of predictive marker for chemotherapy response

- Development and validation criteria for chemotherapy response in patient-derived patient-derived xenograft models and spheroid culture models, that can predict patient clinical outcome

- Development of predictive markers for chemotherapy response

- Quantitative, qualitative and genetic mutation tests using plasma-derived cell-free DNA can minimize invasive sampling and overcome the limitations of molecular genetic testing in patients with difficult tissue access.

- By using cell-free DNA, continuous samples can be collected and used as a monitoring model for cancer progress, treatment progress, and therapeutic response.

- The study of circulating cell-free DNA isolated from blood samples of patients can provide basic data for the early diagnosis of pancreatic cancer and the prognosis of future pancreatic cancer by studying the gene mutation and expression patterns showing pancreatic cancer-specific changes has.

(출처 : SUMMARY 6p)

목차 Contents

• 표지 ... 1
• 국문 요약문 ... 3
• SUMMARY ... 6
• 목차 ... 9
• I. 총괄과제 ... 11
• 1. 연구개발과제의 개요 ... 12
• 2. 국내외 기술개발 현황 ... 20
• 3. 연구수행 내용 및 결과 ... 22
• 4. 목표달성도 및 관련분야 기여도 ... 57
• 5. 연구결과의 활용계획 ... 60
• 6. 연구과정에서 수집한 해외과학기술정보 ... 61
• 7. 연구개발과제의 대표적 연구실적 ... 62
• 8. 참여연구원 현황 ... 63
• 9. 기타사항 ... 65
• 10. 참고문헌 ... 65
• II. 제 1 세부과제 ... 70
• 1. 연구개발과제의 개요 ... 71
• 2. 국내외 기술개발 현황 ... 72
• 3. 연구수행 내용 및 결과 ... 72
• 4. 목표달성도 및 관련분야 기여도 ... 80
• 5. 연구결과의 활용계획 ... 81
• 6. 연구과정에서 수집한 해외과학기술정보 ... 81
• 7. 연구개발과제의 대표적 연구실적 ... 82
• 8. 참여연구원 현황 ... 82
• 9. 기타사항 ... 83
• 10. 참고문헌 ... 83
• III. 제 2 세부과제 ... 86
• 1. 연구개발과제의 개요 ... 87
• 2. 국내외 기술개발 현황 ... 91
• 3. 연구수행 내용 및 결과 ... 91
• 4. 목표달성도 및 관련분야 기여도 ... 105
• 5. 연구결과의 활용계획 ... 106
• 6. 연구과정에서 수집한 해외과학기술정보 ... 107
• 7. 연구개발과제의 대표적 연구실적 ... 107
• 8. 참여연구원 현황 ... 108
• 9. 기타사항 ... 109
• 10. 참고문헌 ... 109
• IV. 제 3 세부과제 ... 110
• 1. 연구개발과제의 개요 ... 111
• 2. 국내외 기술개발 현황 ... 113
• 3. 연구수행 내용 및 결과 ... 115
• 4. 목표달성도 및 관련분야 기여도 ... 129
• 5. 연구결과의 활용계획 ... 129
• 6. 연구과정에서 수집한 해외과학기술정보 ... 130
• 7. 연구개발과제의 대표적 연구실적 ... 131
• 8. 참여연구원 현황 ... 132
• 9. 기타사항 ... 132
• 10. 참고문헌 ... 132
• 끝페이지 ... 134