Abstract：
:Small molecule inhibitors target specific metabolic pathways in tumor cells and are a promising class of drugs for the treatment of cancers. The best known example is the treatment of chronic myeloid leukemia (CML) with Gleevec. This is a small molecule inhibitor of the Bcr-Abl kinase which has been shown to drive the initiation and progression of CML. While treatment of early stage CML with Gleevec has been quite successful, later stages of the disease (blast crisis) are not successfully treated due to the emergence of drug resistant cells. It is therefore important to understand the principles according to which drug resistant cells evolve, so that we can design treatment strategies which aim to prevent the rise of resistant cells. Such evolutionary dynamics can be studied with mathematical models, and this article reviews such an approach. We address three specific questions: (i) Do resistant cells emerge before or after the start of therapy? (ii) How does the turnover rate of cancer cells influence the evolution of drug resistant cells? (iii) Can combination therapy be used to prevent drug resistance? We apply our model to the treatment of CML with Gleevec, in order to demonstrate how this mathematical framework can be applied to the treatment of a specific cancer with small molecule inhibitors.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Wodarz D,Komarova NLdoi
10.1016/j.semcancer.2005.07.002keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
506-14issue
6eissn
1044-579Xissn
1096-3650pii
S1044-579X(05)00044-1journal_volume
15pub_type
杂志文章,评审abstract：:While the centrality of aberrant cell proliferation in cancer was widely acknowledged long ago, it is only recently that the control of cell death has been recognized as an important target in carcinogenesis. Various lines of evidence now suggest that p53 is a positive regulator of cell death, and particularly of apop...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-06-01 00:00:00
abstract：:Malignant cancer cells do not act as lone wolves to achieve metastasis, as they exist within a complex ecosystem consisting of an extracellular matrix scaffold populated by carcinoma-associated fibroblasts (CAFs), endothelial cells and immune cells. We recognize local (primary tumor) and distant ecosystems (metastasis...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2013.12.009
更新日期：2014-04-01 00:00:00
abstract：:The biology and the pathology of the stress-activated protein kinases (SAPKs; p38s and c-Jun-NH(2)-terminal kinases (JNKs)) are somewhat confusing. In some systems, these enzymes augment cell proliferation whereas in other cells they support growth arrest and tumor suppressing activity. Similarly, in some types of can...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2004.04.006
更新日期：2004-08-01 00:00:00
abstract：:Malignant mesothelioma, a tumor of the pleura, pericardium, and peritoneum, is presently a worldwide problem. Current therapy is ineffective in slowing the course of the disease, and median survival from the time of diagnosis is rarely greater than 1 year. While the tumor was almost unknown prior to the second half of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0347
更新日期：2001-02-01 00:00:00
abstract：:Large-scale sequencing methodologies have helped us identify numerous genomic alterations and we have started to scratch the surface of many new targets for treatment of cancer and the associated predictive biomarkers. TRAIL (TNF-related apoptosis-inducing ligand) is a highly appreciated anti-cancer molecule because o...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.01.007
更新日期：2019-10-01 00:00:00
abstract：:While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.03.004
更新日期：2017-04-01 00:00:00
abstract：:Nucleotide sequence analysis at five distinct loci across the 140, 000 bp genomes of more than 60 KSHV samples from KS and PEL tumors from North America, Africa, the Middle East, Asia and the Pacific revealed that they cluster into four major subtypes (A, B, C and D) that have close associations with the geographic an...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0116
更新日期：1999-06-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.08.011
更新日期：2020-09-03 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2006.10.005
更新日期：2007-02-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.08.012
更新日期：2020-09-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.02.005
更新日期：2019-10-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.10.004
更新日期：2020-10-19 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-12-01 00:00:00
abstract：:Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.006
更新日期：2020-04-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-10-01 00:00:00
abstract：:Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation a...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.06.001
更新日期：2017-08-01 00:00:00
abstract：:The growth regulatory functions of a family of structurally related polypeptides are mediated through the membrane-bound epidermal growth factor receptor molecule. This ligand family includes epidermal growth factor, transforming growth factor-alpha, amphiregulin, and polypeptides encoded by several poxviruses. The st...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1990-08-01 00:00:00
abstract：:The dysregulation of apoptosis is a key step in developing cancers, and mediates resistance to cancer therapy. Commitment to apoptosis is caused by permeabilization of the outer mitochondrial membrane, a process regulated by the interactions between different proteins of Bcl-2 family. Furthermore, Bcl-2 family protein...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2013.08.008
更新日期：2013-12-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.09.001
更新日期：2020-02-01 00:00:00
abstract：:Chronic lymphocytic leukaemia (CLL) is the most common form of lymphoid malignancy in Western countries, accounting for around a quarter of all leukaemias. Evidence from epidemiological and family studies have provided evidence for familial clustering of CLL compatible with inherited genetic predisposition to CLL. Dir...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.08.006
更新日期：2010-12-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2015.09.004
更新日期：2016-02-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2014.04.010
更新日期：2014-10-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2005.06.006
更新日期：2005-10-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2006.02.002
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1995.0005
更新日期：1995-02-01 00:00:00
abstract：:While current treatment regimens for acute leukemia can dramatically improve patient survival, there remains room for improvement. Due to its roles in cell differentiation, cell survival, and apoptotic signaling, modulation of the cyclic AMP (cAMP) pathway has provided a meaningful target in hematological malignancies...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.02.004
更新日期：2020-02-07 00:00:00
abstract：:Laminins are a growing family of alphabetagamma heterotrimeric proteins, commonly found in basement membranes (BMs). These large molecules promote cell adhesion and migration via integrins and other cell-surface receptors. Over 12 laminin isoforms are presently known. The various isoforms have a cell- and tissue-speci...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/S1044-579X(02)00023-8
更新日期：2002-06-01 00:00:00
abstract：:T cell acute leukaemias involve a number of different classes of oncogenes. A group of such genes is the RBTN family located on chromosomes 11 and 12. Two members of this family, RBTN1/Ttg-1 and RBTN2/Ttg-2, are located near recurring T cell acute lymphocytic leukaemia-associated translocations. Chromosomal translocat...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1993-12-01 00:00:00
abstract：:DNA damaging agents (ionizing radiation and chemotherapeutics) are considered as most effective in cancer treatment. However, there is a subpopulation of carcinoma cells within the tumour demonstrating resistance to DNA damaging treatment approaches. It is suggested that limited tumour response to this kind of therapy...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2014.06.002
更新日期：2015-04-01 00:00:00
abstract：:The anaphase promoting complex/ cyclosome (APC/C), is an evolutionarily conserved protein complex essential for cellular division due to its role in regulating the mitotic transition from metaphase to anaphase. In this review, we highlight recent work that has shed light on our understanding of the role of APC/C coact...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.03.001
更新日期：2020-12-01 00:00:00
