Successful therapy must eradicate cancer stem cells

被引:192
作者
Dingli, David
Michor, Franziska
机构
[1] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA
[2] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA
关键词
hematopoiesis; cancer; cancer stem cell; mathematical modeling; therapy;
D O I
10.1634/stemcells.2006-0136
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Despite significant improvements in cancer therapy, tumor recurrence is frequent and can be due to a variety of mechanisms, including the evolution of resistance and tumor progression. Cancer stem cells have been postulated to maintain tumor growth similar to normal stem cells maintaining tissue homeostasis. Recently, the existence of these malignant stem cells has been proven for hematological as well as some solid tumors. Tumor stem cells are not targeted by standard therapy and might be responsible for treatment failure and tumor recurrence in many patients. We designed a simple mathematical model to demonstrate the importance of eliminating tumor stem cells. We explored different therapeutic scenarios to illustrate the properties required from novel therapeutic agents for successful tumor treatment. We show that successful therapy must eradicate tumor stem cells.
引用
收藏
页码:2603 / 2610
页数:8
相关论文
共 63 条
[1]   Evidence that the number of hematopoietic stem cells per animal is conserved in mammals [J].
Abkowitz, JL ;
Catlin, SN ;
McCallie, MT ;
Guttorp, P .
BLOOD, 2002, 100 (07) :2665-2667
[2]   BEHAVIOR OF HEMATOPOIETIC STEM-CELLS IN A LARGE ANIMAL [J].
ABKOWITZ, JL ;
PERSIK, MT ;
SHELTON, GH ;
OTT, RL ;
KIKLEVICH, JV ;
CATLIN, SN ;
GUTTORP, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (06) :2031-2035
[3]   EVIDENCE FOR THE MAINTENANCE OF HEMATOPOIESIS IN A LARGE ANIMAL BY THE SEQUENTIAL ACTIVATION OF STEM-CELL CLONES [J].
ABKOWITZ, JL ;
LINENBERGER, ML ;
NEWTON, MA ;
SHELTON, GH ;
OTT, RL ;
GUTTORP, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (22) :9062-9066
[4]  
Armitage P., 1957, BR J CANC, V11
[5]  
ARMITAGE P, 1954, BR J CANC, V8
[6]   AIDA (all-trans retinoic acid plus idarubicin) in newly diagnosed acute promyelocytic leukemia: A Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Pilot study [J].
Avvisati, G ;
LoCoco, F ;
Diverio, D ;
Falda, M ;
Ferrara, F ;
Lazzarino, M ;
Russo, D ;
Petti, MC ;
Mandelli, F .
BLOOD, 1996, 88 (04) :1390-1398
[7]   Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells [J].
Beyne-Rauzy, O ;
Recher, C ;
Dastugue, N ;
Demur, C ;
Pottier, G ;
Laurent, G ;
Sabatier, L ;
Mansat-De Mas, V .
ONCOGENE, 2004, 23 (45) :7507-7516
[8]   Timed sequential therapy of acute myelogenous leukemia in adults:: a phase II study of retinoids in combination with the sequential administration of cytosine arabinoside, idarubicin and etoposide [J].
Bolaños-Meade, J ;
Karp, JE ;
Guo, CF ;
Sarkodee-Adoo, CB ;
Rapoport, AP ;
Tidwell, ML ;
Buddharaju, LN ;
Chen, TT .
LEUKEMIA RESEARCH, 2003, 27 (04) :313-321
[9]   EXPRESSION AND ACTIVITY OF P-GLYCOPROTEIN, A MULTIDRUG EFFLUX PUMP, IN HUMAN HEMATOPOIETIC STEM-CELLS [J].
CHAUDHARY, PM ;
RONINSON, IB .
CELL, 1991, 66 (01) :85-94
[10]   A mathematical model of hematopoiesis - I. Periodic chronic myelogenous leukemia [J].
Colijn, C ;
Mackey, MC .
JOURNAL OF THEORETICAL BIOLOGY, 2005, 237 (02) :117-132