胰腺癌精准治疗：从小众走向主流

罗国培; 虞先濬

doi:10.19401/j.cnki.1007-3639.2022.10.004

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- 胰腺癌精准治疗：从小众走向主流
- Precision therapy in pancreatic cancer: from streamlet towards mainstream
- 中国癌症杂志 2022年32卷第10期页码：960-970
- 作者机构：
  
  1. 复旦大学附属肿瘤医院胰腺外科，复旦大学胰腺肿瘤研究所，上海市胰腺肿瘤研究所，复旦大学上海医学院肿瘤学系，上海 200032
  2. Pancreatic Cancer Institute, Fudan University
  3. Shanghai Pancreatic Cancer Institute
  4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- 作者简介：
  
  [ "罗国培（ORCID: 0000-0002-6582-9624），博士，副主任医师，研究员。" ]
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.10.004
  中图分类号： R735.9
- 收稿：2022-06-29，
  
  修回：2022-10-18，
  
  网络出版：2022-10-30，
- 稿件说明：
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罗国培, 虞先濬. 胰腺癌精准治疗：从小众走向主流[J]. 中国癌症杂志, 2022,32(10):960-970.

Guopei LUO, Xianjun YU. Precision therapy in pancreatic cancer: from streamlet towards mainstream[J]. China Oncology, 2022, 32(10): 960-970.
罗国培, 虞先濬. 胰腺癌精准治疗：从小众走向主流[J]. 中国癌症杂志, 2022,32(10):960-970. DOI： 10.19401/j.cnki.1007-3639.2022.10.004.

Guopei LUO, Xianjun YU. Precision therapy in pancreatic cancer: from streamlet towards mainstream[J]. China Oncology, 2022, 32(10): 960-970. DOI： 10.19401/j.cnki.1007-3639.2022.10.004.

摘要

胰腺癌恶性程度高，预后差，治疗手段有限，精准治疗是提高胰腺癌患者疗效的大势所趋。超过1/4的胰腺癌患者存在可治疗的靶点，主要包括

KRAS

突变、同源重组修复缺陷、融

合基因改变、免疫微环境等四大类分子靶标，其中有恶性肿瘤家族史或个人史、年轻患者及腺泡细胞癌等胰腺癌患者更可能从精准治疗中获益。然而目前胰腺癌患者最终接受精准治疗的不足4%，肿瘤分子谱检测每有

KRAS

突变状态、肿瘤细胞含量、融合基因、胚系突变等关键信息缺失，精准治疗仍是一种小众治疗手段。因而有必要建立精准检测技术规范，打造专业化的精准分析团队，强调多中心协作从而积累循证医学证据，推动胰腺癌精准治疗从小众走向主流，造福于广大胰腺癌患者。最新的研究结果表明，胰腺癌精准治疗可改善患者预后，延长生存期。2019年，《新英格兰医学杂志》（

New England Journal of Medicine

）报道了针对具有

BRCA

1或

BRCA

2胚系突变的晚期胰腺癌进行多聚二磷酸腺苷核糖聚合酶[poly (ADP-ribose) polymerase，PARP

]

抑制剂奥拉帕利维持治疗的POLO研究，从而拉开了胰腺癌精准治疗的序幕。2020年，得克萨斯大学MD安德森癌症中心（The University of Texas MD Anderson Cancer Center）Pishvaian等报道了“知道您的肿瘤（Know Your Tumor，KYT）”计划。结果表明，在1 856例胰腺癌患者中，具有可治疗靶点且匹配对应治疗的患者（46例，中位生存期为2.58年）其预后明显优于具有可治疗靶点但未匹配对应治疗的患者[143例，中位生存期为1.51年，风险比（hazard ratio，HR） = 0.42，

= 0.004

]

以及无可治疗靶点的患者（488例，中位生存期为1.32年，HR = 0.34，

0.000 1）。然而，具有可治疗靶点但未匹配对应治疗的患者的预后却与无可治疗靶点的患者差异无统计学意义（

= 0.10）。这项真实世界研究表明，对有可治疗靶点的胰腺癌实施精准治疗可将胰腺癌患者的生存期延长1年以上。目前胰腺癌精准治疗的靶标包括

KRAS

突变状态（

KRAS

野生型，

KRAS G

突变）、同源重组修复缺陷（

BRCA

1/2、

PALB

2、

ATM

ATR

ATRX

、

CHEK

2、

CDK

12、

RAD

51、

NBN

、

BLM

、

FANC

、

RAD

51/51

、

RAD

50、

BAP

1、

BARD

1、

BRIP

1和

MRE

11）、融合基因改变（

NTRK

、

NRG

1、

ALK

、

RAF

、

RET

、

MET

、

FGFR

2/3和

ROS

）、免疫微环境[

MSI

、

TMB

和

MMR

（

MLH

1、

MLH

3、

MSH

2、

MSH

3、

MSH

6、

PMS

1、

PMS

2、

POLE

和

EPCAM

）

]

、其他[

BRAF

、人表皮生长因子受体2（human epidermal growth factor receptor 2，

HER

2）

]

等。由于胰腺癌精准治疗靶点相对有限且分布不集中，患者存在生存期短以及标本难获得等劣势，因而有必要建立专业化的精准分析团队，进而推动胰腺癌精准治疗的发展。相信随着业内对精准治疗的重视，胰腺癌的精准治疗必将迎来春天。

Abstract

Pancreatic cancer is a highly dismal malignancy and has a poor response to major treatments. Patients with pancreatic cancer usually have poor prognosis. Precision therapy has a great potential to improve the outcome of pancreatic cancer. Over 25% of patients have druggable targets

which mainly involve in

KRAS

mutation status

homologous recombination repair deficiency

gene fusions

and immunotherapy related pathways. Patients with familial or personal history of malignancy

younger patients

or patients with acinar cell carcinoma may benefit from precision therapy. However

only 4% of patients have received precision therapy

and thus precision therapy is still not a major therapeutic method for pancreatic cancer. It is common that genetic/molecular reports are lack of critical information

such as

KRAS

mutation status

tumor cell content

fusions and germline mutations. It is necessary to promote precision therapy from streamlet towards mainstream by formulating detection technique

establishing expertise team and stressing cooperation to accumulate evidence

thereby providing benefits for the patients. Recent reports have shown that precision treatments could improve the outcome and survival of patients with pancreatic cancer. In 2019

The

New England Journal of Medicine

published the POLO study which investigated olaparib

an inhibitor of poly (ADP-ribose) polymerase (PARP)

in patients with metastatic pancreatic cancer and

BRCA

1 or

BRCA

2 germline mutation. This is the first clinical trial of precision therapy based on therapeutic targets in pancreatic cancer. In 2020

Pishvaian et al. from the University of Texas MD Anderson Cancer Center published the results of “Know Your Tumor (KYT)”. In this study

among 1 856 patients with pa

ncreatic cancer

patients with actionable molecular alterations who received a matched therapy (

= 46

2.58 years) had longer median overall survival than did those patients who only received unmatched therapies [

= 143; 1.51 years; hazard ratio (HR) was 0.42

= 0.004

]

. The patients who received a matched therapy also had longer overall survival compared with the patients who did not have an actionable molecular alteration (

=488; 1.32 years; HR was 0.34

0.000 1). This real-world study indicates that matched treatments for patients with pancreatic cancer and actionable molecular alterations could prolong the overall survival of patients for more than one year. To date

therapeutic targets in pancreatic cancer include

KRAS

mutation status (

KRAS

wild-type and

KRAS G

mutation)

homologous recombination repair deficiency (

BRCA

1/2

PALB

ATM

ATR

ATRX

CHEK

CDK

RAD

NBN

BLM

FANC

RAD

51/51

RAD

BAP

BARD

BRIP

MRE

11)

gene fusions (

NTRK

NRG

ALK

RAF

RET

MET

FGFR

2/3

ROS

)

immunotherapy related pathways [

MSI

TMB

MMR

(

MLH

MSH

PMS

POLE

EPCAM

)

]

and others [

BRAF

human epidermal growth factor receptor 2 (

HER

]

. It is necessary to establish specialized team which focuses on precision treatments in pancreatic cancer for the reasons that only limited proportion of patients have therapeutic targets which are widely distributed. The overall survival of patients with pancreatic cancer is poor. It is hard to acquire tumor specimens from advanced pancreatic cancer. As great importance has been attached

we believe that there will be a bright future for the precision treatment in pancreatic cancer.

关键词

Keywords

references

HAYASHI A , HONG J , IACOBUZIO-DONAHUE C A . The pancreatic cancer genome revisited [J ] . Nat Rev Gastroenterol Hepatol , 2021 , 18 ( 7 ): 469 - 481 . DOI: 10.1038/s41575-021-00463-z http://doi.org/10.1038/s41575-021-00463-z

朱鑫哲 , 李浩 , 徐华祥 , 等 . 2021年胰腺癌研究及诊疗新进展 [J ] . 中国癌症杂志 , 2022 , 32 ( 1 ): 1 - 12 . DOI: 10.19401/j.cnki.1007-3639.2022.01.001 http://doi.org/10.19401/j.cnki.1007-3639.2022.01.001

ZHU X Z , LI H , XU H X , et al. Advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2021 [J ] . China Oncol , 2022 , 32 ( 1 ): 1 - 12 .

QIAN Y Z , GONG Y T , FAN Z Y , et al. Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma [J ] . J Hematol Oncol , 2020 , 13 ( 1 ): 130 . DOI: 10.1186/s13045-020-00958-3 http://doi.org/10.1186/s13045-020-00958-3 https://doi.org/10.1186/s13045-020-00958-3 https://doi.org/10.1186/s13045-020-00958-3

雷洋洋 , 王小林 . “精准医学”模式下胰腺癌防治的探索与进展 [J ] . 复旦学报(医学版) , 2021 , 48 ( 2 ): 255 - 260 .

LEI Y Y , WANG X L . Exploration and progress in prevention and treatment of pancreatic cancer under the “precision medicine” model [J ] . Fudan Univ J Med Sci , 2021 , 48 ( 2 ): 255 - 260 .

GOLAN T , HAMMEL P , RENI M , et al. Maintenance olaparib for germline BRCA -mutated metastatic pancreatic cancer [J ] . N Engl J Med , 2019 , 381 ( 4 ): 317 - 327 . DOI: 10.1056/NEJMoa1903387 http://doi.org/10.1056/NEJMoa1903387 http://www.nejm.org/doi/10.1056/NEJMoa1903387 http://www.nejm.org/doi/10.1056/NEJMoa1903387

PISHVAIAN M J , BLAIS E M , BRODY J R , et al. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial [J ] . Lancet Oncol , 2020 , 21 ( 4 ): 508 - 518 . DOI : S1470-2045(20)30074-7 http://doi.org/S1470-2045(20)30074-7

PISHVAIAN M J , BENDER R J , HALVERSON D , et al. Molecular profiling of patients with pancreatic cancer: initial results from the Know Your Tumor initiative [J ] . Clin Cancer Res , 2018 , 24 ( 20 ): 5018 - 5027 . DOI: 10.1158/1078-0432.CCR-18-0531 http://doi.org/10.1158/1078-0432.CCR-18-0531

KLEEFF J , MICHALSKI C W . Precision oncology for pancreatic cancer in real-world settings [J ] . Lancet Oncol , 2020 , 21 ( 4 ): 469 - 471 . DOI: S1470-2045(20)30148-0 http://doi.org/S1470-2045(20)30148-0

AUNG K L , FISCHER S E , DENROCHE R E , et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial [J ] . Clin Cancer Res , 2018 , 24 ( 6 ): 1344 - 1354 . DOI: 10.1158/1078-0432.CCR-17-2994 http://doi.org/10.1158/1078-0432.CCR-17-2994

CHANTRILL L A , NAGRIAL A M , WATSON C , et al. Precision medicine for advanced pancreas cancer: the individualized molecular pancreatic cancer therapy (IMPaCT) trial [J ] . Clin Cancer Res , 2015 , 21 ( 9 ): 2029 - 2037 . DOI: 10.1158/1078-0432.CCR-15-0426 http://doi.org/10.1158/1078-0432.CCR-15-0426

LOWERY M A , JORDAN E J , BASTURK O , et al. Real-time genomic profiling of pancreatic ductal adenocarcinoma: potential actionability and correlation with clinical phenotype [J ] . Clin Cancer Res , 2017 , 23 ( 20 ): 6094 - 6100 . DOI: 10.1158/1078-0432.CCR-17-0899 http://doi.org/10.1158/1078-0432.CCR-17-0899

DING D , JAVED A A , CUNNINGHAM D , et al. Challenges of the current precision medicine approach for pancreatic cancer: a single institution experience between 2013 and 2017 [J ] . Cancer Lett , 2021 , 497 : 221 - 228 . DOI: 10.1016/j.canlet.2020.10.039 http://doi.org/10.1016/j.canlet.2020.10.039

NCCN Guidelines Version 1. 2022 . Pancreatic Adenocarcinoma .

SCHULTHEIS B , REUTER D , EBERT M P , et al. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase Ⅱb study [J ] . Ann Oncol , 2017 , 28 ( 10 ): 2429 - 2435 . DOI: 10.1093/annonc/mdx343 http://doi.org/10.1093/annonc/mdx343 https://linkinghub.elsevier.com/retrieve/pii/S0923753419349476 https://linkinghub.elsevier.com/retrieve/pii/S0923753419349476

QIN S K , BAI Y X , WANG Z S , et al. Nimotuzumab combined with gemcitabine versus gemcitabine in KRAS wild-type locally advanced or metastatic pancreatic cancer: a prospective, randomized-controlled, double-blinded, multicenter, and phase Ⅲ clinical trial [C ] . 2022 ASCO Annual Meeting. Abstract LBA4011 .

FUSCO M J , SAEED-VAFA D , CARBALLIDO E M , et al. Identification of targetable gene fusions and structural rearrangements to foster precision medicine in KRAS wild-type pancreatic cancer [J ] . JCO Precis Oncol , 2021 , 5 : PO.20.00265 .

CANON J , REX K , SAIKI A Y , et al. The clinical KRAS (G12C) inhibitor AMG 510 drives anti-tumour immunity [J ] . Nature , 2019 , 575 ( 7781 ): 217 - 223 . DOI: 10.1038/s41586-019-1694-1 http://doi.org/10.1038/s41586-019-1694-1 https://doi.org/10.1038/s41586-019-1694-1 https://doi.org/10.1038/s41586-019-1694-1

SKOULIDIS F , LI B T , DY G K , et al. Sotorasib for lung cancers with KRAS p.G12C mutation [J ] . N Engl J Med , 2021 , 384 ( 25 ): 2371 - 2381 . DOI: 10.1056/NEJMoa2103695 http://doi.org/10.1056/NEJMoa2103695 http://www.nejm.org/doi/10.1056/NEJMoa2103695 http://www.nejm.org/doi/10.1056/NEJMoa2103695

LEIDNER R , SANJUAN SILVA N , HUANG H Y , et al. Neoantigen T-cell receptor gene therapy in pancreatic cancer [J ] . N Engl J Med , 2022 , 386 ( 22 ): 2112 - 2119 . DOI: 10.1056/NEJMoa2119662 http://doi.org/10.1056/NEJMoa2119662 http://www.nejm.org/doi/10.1056/NEJMoa2119662 http://www.nejm.org/doi/10.1056/NEJMoa2119662

MELIEF C J M . T-cell immunotherapy against mutant KRAS for pancreatic cancer [J ] . N Engl J Med , 2022 , 386 ( 22 ): 2143 - 2144 . DOI: 10.1056/NEJMe2204283 http://doi.org/10.1056/NEJMe2204283 http://www.nejm.org/doi/10.1056/NEJMe2204283 http://www.nejm.org/doi/10.1056/NEJMe2204283

CAO L W , HUANG C , CUI ZHOU D , et al. Proteogenomic characterization of pancreatic ductal adenocarcinoma [J ] . Cell , 2021 , 184 ( 19 ): 5031 - 5052 .e26. DOI: 10.1016/j.cell.2021.08.023 http://doi.org/10.1016/j.cell.2021.08.023

ESER S , REIFF N , MESSER M , et al. Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer [J ] . Cancer Cell , 2013 , 23 ( 3 ): 406 - 420 . DOI: 10.1016/j.ccr.2013.01.023 http://doi.org/10.1016/j.ccr.2013.01.023 https://linkinghub.elsevier.com/retrieve/pii/S1535610813000433 https://linkinghub.elsevier.com/retrieve/pii/S1535610813000433

KO A H , BEKAII-SAAB T , VAN ZIFFLE J , et al. A multicenter, open-label phase Ⅱ clinical trial of combined MEK plus EGFR inhibition for chemotherapy-refractory advanced pancreatic adenocarcinoma [J ] . Clin Cancer Res , 2016 , 22 ( 1 ): 61 - 68 . DOI: 10.1158/1078-0432.CCR-15-0979 http://doi.org/10.1158/1078-0432.CCR-15-0979 https://aacrjournals.org/clincancerres/article/22/1/61/248154/A-Multicenter-Open-Label-Phase-II-Clinical-Trial https://aacrjournals.org/clincancerres/article/22/1/61/248154/A-Multicenter-Open-Label-Phase-II-Clinical-Trial

GOLAN T , KHVALEVSKY E Z , HUBERT A , et al. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients [J ] . Oncotarget , 2015 , 6 ( 27 ): 24560 - 24570 . DOI: 10.18632/oncotarget.4183 http://doi.org/10.18632/oncotarget.4183 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.4183 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.4183

BAILEY P , CHANG D K , NONES K , et al. Genomic analyses identify molecular subtypes of pancreatic cancer [J ] . Nature , 2016 , 531 ( 7592 ): 47 - 52 . DOI: 10.1038/nature16965 http://doi.org/10.1038/nature16965 https://doi.org/10.1038/nature16965 https://doi.org/10.1038/nature16965

GOLAN T , O'KANE G M , DENROCHE R E , et al. Genomic features and classification of homologous recombination deficient pancreatic ductal adenocarcinoma [J ] . Gastroenterology , 2021 , 160 ( 6 ): 2119 - 2132 .e9. DOI: 10.1053/j.gastro.2021.01.220 http://doi.org/10.1053/j.gastro.2021.01.220 https://linkinghub.elsevier.com/retrieve/pii/S0016508521003267 https://linkinghub.elsevier.com/retrieve/pii/S0016508521003267

楼文晖 . 胰腺癌精准治疗现状、挑战和未来 [J ] . 中国实用外科杂志 , 2021 , 41 ( 9 ): 1014 - 1016 .

LOU W H . The current status, challenge, and future of precision treatment for pancreatic cancer [J ] . Chin J Pract Surg , 2021 , 41 ( 9 ): 1014 - 1016 .

LAI Z W , GOLAN T , KINDLER H L , et al. POLO: Homologous recombination repair gene mutations (HRRm) in metastatic pancreatic cancer (mPaC) tumors [J ] . Cancer Res , 2020 , 80 ( < W > 16 suppl): Abstract nr CT217.

USON P L S Jr , SAMADDER N J , RIEGERT-JOHNSON D , et al. Clinical impact of pathogenic germline variants in pancreatic cancer: results from a multicenter, prospective, universal genetic testing study [J ] . Clin Transl Gastroenterol , 2021 , 12 ( 10 ): e00414 . DOI: 10.14309/ctg.0000000000000414 http://doi.org/10.14309/ctg.0000000000000414 https://journals.lww.com/10.14309/ctg.0000000000000414 https://journals.lww.com/10.14309/ctg.0000000000000414

PISHVAIAN M J , BLAIS E M , BRODY J R , et al. Outcomes in patients with pancreatic adenocarcinoma with genetic mutations in DNA damage response pathways: results from the Know Your Tumor program [J ] . JCO Precis Oncol , 2019 , 3 : 1 - 10 . DOI: 10.1200/PO.19.00115 http://doi.org/10.1200/PO.19.00115

HEINING C , HORAK P , UHRIG S , et al. NRG 1 fusions in KRAS wild-type pancreatic cancer [J ] . Cancer Discov , 2018 , 8 ( 9 ): 1087 - 1095 . DOI: 10.1158/2159-8290.CD-18-0036 http://doi.org/10.1158/2159-8290.CD-18-0036 https://aacrjournals.org/cancerdiscovery/article/8/9/1087/10152/NRG1-Fusions-in-KRAS-Wild-Type-Pancreatic https://aacrjournals.org/cancerdiscovery/article/8/9/1087/10152/NRG1-Fusions-in-KRAS-Wild-Type-Pancreatic

LAETSCH T W , DUBOIS S G , MASCARENHAS L , et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 s tudy [J ] . Lancet Oncol , 2018 , 19 ( 5 ): 705 - 714 . DOI: 10.1016/S1470-2045(18)30119-0 http://doi.org/10.1016/S1470-2045(18)30119-0 https://linkinghub.elsevier.com/retrieve/pii/S1470204518301190 https://linkinghub.elsevier.com/retrieve/pii/S1470204518301190

LAWLOR R T , MATTIOLO P , MAFFICINI A , et al. Tumor mutational burden as a potential biomarker for immunotherapy in pancreatic cancer: systematic review and still-open questions [J ] . Cancers (Basel) , 2021 , 13 ( 13 ): 3119 . DOI: 10.3390/cancers13133119 http://doi.org/10.3390/cancers13133119 https://www.mdpi.com/2072-6694/13/13/3119 https://www.mdpi.com/2072-6694/13/13/3119

LE D T , URAM J N , WANG H , et al. PD-1 blockade in tumors with mismatch-repair deficiency [J ] . N Engl J Med , 2015 , 372 ( 26 ): 2509 - 2520 . DOI: 10.1056/NEJMoa1500596 http://doi.org/10.1056/NEJMoa1500596 http://www.nejm.org/doi/10.1056/NEJMoa1500596 http://www.nejm.org/doi/10.1056/NEJMoa1500596

HU Z I , SHIA J R , STADLER Z K , et al. Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations [J ] . Clin Cancer Res , 2018 , 24 ( 6 ): 1326 - 1336 . DOI: 10.1158/1078-0432.CCR-17-3099 http://doi.org/10.1158/1078-0432.CCR-17-3099

KURZ E , HIRSCH C A , DALTON T , et al. Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer [J ] . Cancer Cell , 2022 , 40 ( 7 ): 720 - 737 .e5. DOI: 10.1016/j.ccell.2022.05.006 http://doi.org/10.1016/j.ccell.2022.05.006

ZHU X F , CAO Y S , LIU W Y , et al. Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial [J ] . Lancet Oncol , 2022 , 23 ( 3 ): e105 - e115 . DOI: 10.1016/S1470-2045(22)00066-3 http://doi.org/10.1016/S1470-2045(22)00066-3

HENDIFAR A , BLAIS E M , WOLPIN B , et al. Retrospective case series analysis of RAF family alterations in pancreatic cancer: real-world outcomes from targeted and standard therapies [J ] . JCO Precis Oncol , 2021 , 5 : PO.20.00494 .

AGUIRRE A J , NOWAK J A , CAMARDA N D , et al. Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine [J ] . Cancer Discov , 2018 , 8 ( 9 ): 1096 - 1111 . DOI: 10.1158/2159-8290.CD-18-0275 http://doi.org/10.1158/2159-8290.CD-18-0275

CHOU A , WADDELL N , COWLEY M J , et al. Clinical and molecular characterization of HER2 amplified-pancreatic cancer [J ] . Genome Med , 2013 , 5 ( 8 ): 78 . DOI: 10.1186/gm482 http://doi.org/10.1186/gm482

KLEIN A P , BRUNE K A , PETERSEN G M , et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds [J ] . Cancer Res , 2004 , 64 ( 7 ): 2634 - 2638 .

BRUNE K A , LAU B , PALMISANO E , et al. Importance of age of onset in pancreatic cancer kindreds [J ] . J Natl Cancer Inst , 2010 , 102 ( 2 ): 119 - 126 . DOI: 10.1093/jnci/djp466 http://doi.org/10.1093/jnci/djp466

HU C L , LADUCA H , SHIMELIS H , et al. Multigene hereditary cancer panels reveal high-risk pancreatic cancer susceptibility genes [J ] . JCO Precis Oncol , 2018 , 2. PO. 17. 00291.

VARGHESE A M , SINGH I , SINGH R , et al. Early-onset pancreas cancer: clinical descriptors, genomics, and outcomes [J ] . J Natl Cancer Inst , 2021 , 113 ( 9 ): 1194 - 1202 . DOI: 10.1093/jnci/djab038 http://doi.org/10.1093/jnci/djab038

CHMIELECKI J , HUTCHINSON K E , FRAMPTON G M , et al. Comprehensive genomic profiling of pancreatic acinar cell carcinomas identifies recurrent RAF fusions and frequent inactivation of DNA repair genes [J ] . Cancer Discov , 2014 , 4 ( 12 ): 1398 - 1405 . DOI: 10.1158/2159-8290.CD-14-0617 http://doi.org/10.1158/2159-8290.CD-14-0617 https://aacrjournals.org/cancerdiscovery/article/4/12/1398/4313/Comprehensive-Genomic-Profiling-of-Pancreatic https://aacrjournals.org/cancerdiscovery/article/4/12/1398/4313/Comprehensive-Genomic-Profiling-of-Pancreatic

JIAO Y C , YONESCU R , OFFERHAUS G J , et al. Whole-exome sequencing of pancreatic neoplasms with acinar differentiation [J ] . J Pathol , 2014 , 232 ( 4 ): 428 - 435 . DOI: 10.1002/path.4310 http://doi.org/10.1002/path.4310 https://onlinelibrary.wiley.com/doi/10.1002/path.4310 https://onlinelibrary.wiley.com/doi/10.1002/path.4310

王欢 , 金钢 . 胰腺癌精准治疗的现状和展望 [J ] . 中国普通外科杂志 , 2021 , 30 ( 9 ): 997 - 1005 .

WANG H , JIN G . Current status and future perspective of precision medicine in pancreatic cancer treatment [J ] . Chin J Gen Surg , 2021 , 30 ( 9 ): 997 - 1005 .

COLLISSON E A . Bringing pancreas cancer into the lab [J ] . Cancer Discov , 2018 , 8 ( 9 ): 1062 - 1063 . DOI: 10.1158/2159-8290.CD-18-0811 http://doi.org/10.1158/2159-8290.CD-18-0811

BRAR G , BLAIS E M , JOSEPH BENDER R , et al. Multi-omic molecular comparison of primary versus metastatic pancreatic tumours [J ] . Br J Cancer , 2019 , 121 ( 3 ): 264 - 270 . DOI: 10.1038/s41416-019-0507-5 http://doi.org/10.1038/s41416-019-0507-5 https://doi.org/10.1038/s41416-019-0507-5 https://doi.org/10.1038/s41416-019-0507-5

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