Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy
Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of c...
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| Format: | Article |
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Cold Spring Harbor Laboratory
2018
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| Online Access: | http://hdl.handle.net/1721.1/116972 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1811084437674262528 |
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| author | Pattabiraman, Diwakar R. Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Pattabiraman, Diwakar R. Weinberg, Robert A |
| author_sort | Pattabiraman, Diwakar R. |
| collection | MIT |
| description | Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of carcinomas. First, a majority of deaths from these types of cancers occurs as a result of distant metastases and not the primary tumors themselves. Second, subsets of cells that are able to survive conventional therapy drive the aggressive relapse of the tumors, often in forms that are resistant to treatment. A frequently observed feature of malignant carcinomas is the loss of epithelial traits and the gain of certain mesenchymal ones that are programmed by the cell-biological program termed the epithelial-to-mesenchymal transition (EMT). The EMT program can confer (i) an ability to disseminate, (ii) an ability to become stem-like tumor-initiating cells, (iii) an ability to found new tumor colonies at distant anatomical sites, and (iv) an elevated resistance to therapy. These multiple powers of the EMT program explain why it has become an attractive target for therapeutic intervention. Recent work has revealed the variable nature of the EMT, with multiple versions of the program being observed depending on the tissue context and the stage of tumor progression. In this review, we attempt to crystallize emerging concepts in the research on EMTand stemness and discuss the benefits of using a differentiation-based therapeutic strategy for the eradication of stem-like populations that have adopted various versions of the EMT program. |
| first_indexed | 2024-09-23T12:50:42Z |
| format | Article |
| id | mit-1721.1/116972 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:50:42Z |
| publishDate | 2018 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | dspace |
| spelling | mit-1721.1/1169722022-10-01T11:28:32Z Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy Pattabiraman, Diwakar R. Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Weinberg, Robert A Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of carcinomas. First, a majority of deaths from these types of cancers occurs as a result of distant metastases and not the primary tumors themselves. Second, subsets of cells that are able to survive conventional therapy drive the aggressive relapse of the tumors, often in forms that are resistant to treatment. A frequently observed feature of malignant carcinomas is the loss of epithelial traits and the gain of certain mesenchymal ones that are programmed by the cell-biological program termed the epithelial-to-mesenchymal transition (EMT). The EMT program can confer (i) an ability to disseminate, (ii) an ability to become stem-like tumor-initiating cells, (iii) an ability to found new tumor colonies at distant anatomical sites, and (iv) an elevated resistance to therapy. These multiple powers of the EMT program explain why it has become an attractive target for therapeutic intervention. Recent work has revealed the variable nature of the EMT, with multiple versions of the program being observed depending on the tissue context and the stage of tumor progression. In this review, we attempt to crystallize emerging concepts in the research on EMTand stemness and discuss the benefits of using a differentiation-based therapeutic strategy for the eradication of stem-like populations that have adopted various versions of the EMT program. National Institutes of Health (U.S.) (grant R01 CA078461) National Institutes of Health (U.S.) (grant (P01 CA080111) Samuel Waxman Cancer Research Foundation Massachusetts Institute of Technology. Ludwig Center for Cancer Research 2018-07-13T14:07:57Z 2018-07-13T14:07:57Z 2016 2018-07-12T14:52:12Z Article http://purl.org/eprint/type/JournalArticle 0091-7451 1943-4456 http://hdl.handle.net/1721.1/116972 Pattabiraman, Diwakar R., and Robert A. Weinberg. “Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy.” Cold Spring Harbor Symposia on Quantitative Biology 81 (2016): 11–19. https://orcid.org/0000-0002-0895-3557 http://dx.doi.org/10.1101/SQB.2016.81.030957 Cold Spring Harbor Symposia on Quantitative Biology Creative Commons Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory Press |
| spellingShingle | Pattabiraman, Diwakar R. Weinberg, Robert A Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy |
| title | Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy |
| title_full | Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy |
| title_fullStr | Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy |
| title_full_unstemmed | Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy |
| title_short | Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy |
| title_sort | targeting the epithelial to mesenchymal transition the case for differentiation based therapy |
| url | http://hdl.handle.net/1721.1/116972 https://orcid.org/0000-0002-0895-3557 |
| work_keys_str_mv | AT pattabiramandiwakarr targetingtheepithelialtomesenchymaltransitionthecasefordifferentiationbasedtherapy AT weinbergroberta targetingtheepithelialtomesenchymaltransitionthecasefordifferentiationbasedtherapy |