Designing a broad-spectrum integrative approach for cancer prevention and treatment
Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few dis...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105834 https://orcid.org/0000-0002-6702-4192 |
| _version_ | 1811088151863623680 |
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| author | Vander Heiden, Matthew G. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Vander Heiden, Matthew G. |
| author_sort | Vander Heiden, Matthew G. |
| collection | MIT |
| description | Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. |
| first_indexed | 2024-09-23T13:57:05Z |
| format | Article |
| id | mit-1721.1/105834 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:57:05Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1058342022-09-28T17:20:23Z Designing a broad-spectrum integrative approach for cancer prevention and treatment Vander Heiden, Matthew G. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Vander Heiden, Matthew G. Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. 2016-12-15T19:10:21Z 2016-12-15T19:10:21Z 2015-12 Article http://purl.org/eprint/type/JournalArticle 1044579X http://hdl.handle.net/1721.1/105834 Block, Keith I. et al. “Designing a Broad-Spectrum Integrative Approach for Cancer Prevention and Treatment.” Seminars in Cancer Biology 35 (2015): S276–S304. https://orcid.org/0000-0002-6702-4192 en_US http://dx.doi.org/10.1016/j.semcancer.2015.09.007 Seminars in Cancer Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Vander Heiden, Matthew G. Designing a broad-spectrum integrative approach for cancer prevention and treatment |
| title | Designing a broad-spectrum integrative approach for cancer prevention and treatment |
| title_full | Designing a broad-spectrum integrative approach for cancer prevention and treatment |
| title_fullStr | Designing a broad-spectrum integrative approach for cancer prevention and treatment |
| title_full_unstemmed | Designing a broad-spectrum integrative approach for cancer prevention and treatment |
| title_short | Designing a broad-spectrum integrative approach for cancer prevention and treatment |
| title_sort | designing a broad spectrum integrative approach for cancer prevention and treatment |
| url | http://hdl.handle.net/1721.1/105834 https://orcid.org/0000-0002-6702-4192 |
| work_keys_str_mv | AT vanderheidenmatthewg designingabroadspectrumintegrativeapproachforcancerpreventionandtreatment |