Computational Modeling of Pancreatic Cancer Reveals Kinetics of Metastasis Suggesting Optimum Treatment Strategies

被引:325
作者
Haeno, Hiroshi [6 ,7 ]
Gonen, Mithat [8 ]
Davis, Meghan B. [1 ]
Herman, Joseph M. [1 ,5 ]
Iacobuzio-Donahue, Christine A. [1 ,2 ,3 ,4 ]
Michor, Franziska [6 ,7 ]
机构
[1] Johns Hopkins Univ Hosp, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21231 USA
[3] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21231 USA
[4] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21231 USA
[5] Johns Hopkins Univ Hosp, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21231 USA
[6] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA
[7] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
[8] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
PROGRESSION; CARCINOMA; SURVIVAL; DORMANCY; CHEMOTHERAPY; GEMCITABINE; INSTABILITY; RESECTION; DYNAMICS; PATTERNS;
D O I
10.1016/j.cell.2011.11.060
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pancreatic cancer is a leading cause of cancer-related death, largely due to metastatic dissemination. We investigated pancreatic cancer progression by utilizing a mathematical framework of metastasis formation together with comprehensive data of 228 patients, 101 of whom had autopsies. We found that pancreatic cancer growth is initially exponential. After estimating the rates of pancreatic cancer growth and dissemination, we determined that patients likely harbor metastases at diagnosis and predicted the number and size distribution of metastases as well as patient survival. These findings were validated in an independent database. Finally, we analyzed the effects of different treatment modalities, finding that therapies that efficiently reduce the growth rate of cells earlier in the course of treatment appear to be superior to upfront tumor resection. These predictions can be validated in the clinic. Our interdisciplinary approach provides insights into the dynamics of pancreatic cancer metastasis and identifies optimum therapeutic interventions.
引用
收藏
页码:362 / 375
页数:14
相关论文
共 48 条
[1]  
AMIKURA K, 1995, INT J PANCREATOL, V17, P139
[2]   Mathematical modeling of cancer cell invasion of tissue: biological insight from mathematical analysis and computational simulation [J].
Andasari, Vivi ;
Gerisch, Alf ;
Lolas, Georgios ;
South, Andrew P. ;
Chaplain, Mark A. J. .
JOURNAL OF MATHEMATICAL BIOLOGY, 2011, 63 (01) :141-171
[3]  
[Anonymous], J CLIN ONCOL S
[4]   Neoadjuvant Therapy Is Associated With Improved Survival in Resectable Pancreatic Adenocarcinoma [J].
Artinyan, Avo ;
Anaya, Daniel A. ;
McKenzie, Shaun ;
Ellenhorn, Joshua D. I. ;
Kim, Joseph .
CANCER, 2011, 117 (10) :2044-2049
[5]   PANCREATIC CANCER TUMOR SIZE ON CT SCAN VERSUS PATHOLOGIC SPECIMEN: IMPLICATIONS FOR RADIATION TREATMENT PLANNING [J].
Arvold, Nils D. ;
Niemierko, Andrzej ;
Mamon, Harvey J. ;
Fernandez-del Castillo, Carlos ;
Hong, Theodore S. .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2011, 80 (05) :1383-1390
[6]   Unknown primary tumors metastatic to liver [J].
Ayoub, JP ;
Hess, KR ;
Abbruzzese, MC ;
Lenzi, R ;
Raber, MN ;
Abbruzzese, JL .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (06) :2105-2112
[7]  
Cameron MD, 2000, CANCER RES, V60, P2541
[8]   The patterns and dynamics of genomic instability in metastatic pancreatic cancer [J].
Campbell, Peter J. ;
Yachida, Shinichi ;
Mudie, Laura J. ;
Stephens, Philip J. ;
Pleasance, Erin D. ;
Stebbings, Lucy A. ;
Morsberger, Laura A. ;
Latimer, Calli ;
McLaren, Stuart ;
Lin, Meng-Lay ;
McBride, David J. ;
Varela, Ignacio ;
Nik-Zainal, Serena A. ;
Leroy, Catherine ;
Jia, Mingming ;
Menzies, Andrew ;
Butler, Adam P. ;
Teague, Jon W. ;
Griffin, Constance A. ;
Burton, John ;
Swerdlow, Harold ;
Quail, Michael A. ;
Stratton, Michael R. ;
Iacobuzio-Donahue, Christine ;
Futreal, P. Andrew .
NATURE, 2010, 467 (7319) :1109-1113
[9]   Mathematical oncology: How are the mathematical and physical sciences contributing to the war on breast cancer? [J].
Chauviere A.H. ;
Hatzikirou H. ;
Lowengrub J.S. ;
Frieboes H.B. ;
Thompson A.M. ;
Cristini V. .
Current Breast Cancer Reports, 2010, 2 (3) :121-129
[10]   GEMCITABINE-BASED COMBINATION CHEMOTHERAPY FOLLOWED BY RADIATION WITH CAPECITABINE AS ADJUVANT THERAPY FOR RESECTED PANCREAS CANCER [J].
Desai, Sameer ;
Ben-Josef, Edgar ;
Griffith, Kent A. ;
Simeone, Diane ;
Greenson, Joel K. ;
Francis, Isaac R. ;
Hampton, Janet ;
Colletti, Lisa ;
Chang, Alfred E. ;
Lawrence, Theodore S. ;
Zalupski, Mark M. .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2009, 75 (05) :1450-1455