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
[41]   CLINICAL AND PHARMACOLOGICAL ANALYSIS OF HYPERFRACTIONATED DAILY ORAL ETOPOSIDE [J].
MINAMI, H ;
ANDO, Y ;
SAKAI, S ;
SHIMOKATA, K .
JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (01) :191-199
[42]   MUTATION AND CANCER - A MODEL FOR HUMAN CARCINOGENESIS [J].
MOOLGAVKAR, SH ;
KNUDSON, AG .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1981, 66 (06) :1037-1052
[43]   A NEW THEORY ON THE CANCER-INDUCING MECHANISM [J].
NORDLING, CO .
BRITISH JOURNAL OF CANCER, 1953, 7 (01) :68-72
[44]   Conceptual and practical implications of breast tissue geometry: Toward a more effective, less toxic therapy [J].
Norton, L .
ONCOLOGIST, 2005, 10 (06) :370-381
[45]   PREDICTING COURSE OF GOMPERTZIAN GROWTH [J].
NORTON, L ;
SIMON, R ;
BRERETON, HD ;
BOGDEN, AE .
NATURE, 1976, 264 (5586) :542-545
[46]   The linear process of somatic evolution [J].
Nowak, MA ;
Michor, F ;
Iwasa, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (25) :14966-14969
[47]   Lineage selection and the evolution of multistage carcinogenesis [J].
Nunney, L .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1999, 266 (1418) :493-498
[48]   A mathematical model of drug resistance: Heterogeneous tumors [J].
Panetta, JC .
MATHEMATICAL BIOSCIENCES, 1998, 147 (01) :41-61
[49]   A mechanistic mathematical model of temozolomide myelosuppression in children with high-grade gliomas [J].
Panetta, JC ;
Kirstein, MN ;
Gajjar, AJ ;
Nair, G ;
Fouladi, M ;
Stewart, CF .
MATHEMATICAL BIOSCIENCES, 2003, 186 (01) :29-41
[50]   Imatinib therapy for hypereosinophilic syndrome and eosinophilia-associated myeloproliferative disorders [J].
Pardanani, A ;
Tefferi, A .
LEUKEMIA RESEARCH, 2004, 28 :S47-S52