On the emergence of multifocal cancers
Several tumors can exist as multiple lesions within a tissue. The lesions may either arise independently, or they may be monoclonal. The importance of multiple lesions for tumor staging, progression, and treatment is subject to debate. Here we use mathematical models to analyze the emergence of mult...
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| Format: | Online |
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BioMed Central
2004
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526757/ |
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pubmed-5267572004-11-12 On the emergence of multifocal cancers Wodarz, Dominik Iwasa, Yoh Komarova, Natalia L Research Several tumors can exist as multiple lesions within a tissue. The lesions may either arise independently, or they may be monoclonal. The importance of multiple lesions for tumor staging, progression, and treatment is subject to debate. Here we use mathematical models to analyze the emergence of multiple, clonally related lesions within a single tissue. We refer to them as multi-focal cancers. We find that multifocal cancers can arise through a dynamical interplay between tumor promoting and inhibiting factors. This requires that tumor promoters act locally, while tumor inhibitors act over a longer range. An example of such factors may be angiogenesis promoters and inhibitors. The model further suggests that multifocal cancers represent an intermediate stage in cancer progression as the tumor evolves away from inhibition and towards promotion. Different patterns of progression can be distinguished: (i) If tumor inhibition is strong, the initial growth occurs as a unifocal and self contained lesion; progression occurs through bifurcation of the lesion and this gives rise to multiple lesions. As the tumor continues to evolve and pushes the balance between inhibition and promotion further towards promotion, the multiple lesions eventually give rise to a single large mass which can invade the entire tissue. (ii) If tumor inhibition is weaker upon initiation, growth can occur as a single lesion without the occurrence of multiple lesions, until the entire tissue is invaded. The model suggests that the sum of the tumor sizes across all lesions is the best characteristic which correlates with the stage and metastatic potential of the tumor. BioMed Central 2004-10-01 /pmc/articles/PMC526757/ /pubmed/15461783 http://dx.doi.org/10.1186/1477-3163-3-13 Text en Copyright © 2004 Wodarz et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wodarz, Dominik Iwasa, Yoh Komarova, Natalia L |
| spellingShingle |
Wodarz, Dominik Iwasa, Yoh Komarova, Natalia L On the emergence of multifocal cancers |
| author_facet |
Wodarz, Dominik Iwasa, Yoh Komarova, Natalia L |
| author_sort |
Wodarz, Dominik |
| title |
On the emergence of multifocal cancers |
| title_short |
On the emergence of multifocal cancers |
| title_full |
On the emergence of multifocal cancers |
| title_fullStr |
On the emergence of multifocal cancers |
| title_full_unstemmed |
On the emergence of multifocal cancers |
| title_sort |
on the emergence of multifocal cancers |
| description |
Several tumors can exist as multiple lesions within a tissue. The lesions may either arise independently, or they may be monoclonal. The importance of multiple lesions for tumor staging, progression, and treatment is subject to debate. Here we use mathematical models to analyze the emergence of multiple, clonally related lesions within a single tissue. We refer to them as multi-focal cancers. We find that multifocal cancers can arise through a dynamical interplay between tumor promoting and inhibiting factors. This requires that tumor promoters act locally, while tumor inhibitors act over a longer range. An example of such factors may be angiogenesis promoters and inhibitors. The model further suggests that multifocal cancers represent an intermediate stage in cancer progression as the tumor evolves away from inhibition and towards promotion. Different patterns of progression can be distinguished: (i) If tumor inhibition is strong, the initial growth occurs as a unifocal and self contained lesion; progression occurs through bifurcation of the lesion and this gives rise to multiple lesions. As the tumor continues to evolve and pushes the balance between inhibition and promotion further towards promotion, the multiple lesions eventually give rise to a single large mass which can invade the entire tissue. (ii) If tumor inhibition is weaker upon initiation, growth can occur as a single lesion without the occurrence of multiple lesions, until the entire tissue is invaded. The model suggests that the sum of the tumor sizes across all lesions is the best characteristic which correlates with the stage and metastatic potential of the tumor. |
| publisher |
BioMed Central |
| publishDate |
2004 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526757/ |
| _version_ |
1611369839855665152 |