Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells
Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that futur...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.659963/full |
| _version_ | 1818731624641069056 |
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| author | Scott Sauer Damon R. Reed Damon R. Reed Damon R. Reed Michael Ihnat Robert E. Hurst David Warshawsky Dalit Barkan |
| author_facet | Scott Sauer Damon R. Reed Damon R. Reed Damon R. Reed Michael Ihnat Robert E. Hurst David Warshawsky Dalit Barkan |
| author_sort | Scott Sauer |
| collection | DOAJ |
| description | Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents strategies to target dormant quiescent DTCs that reside at secondary sites. These strategies aim to prevent recurrence by maintaining dormant DTCs at bay, or eradicating them. Various approaches are presented, including: reinforcing the niche where dormant DTCs reside in order to keep dormant DTCs at bay; promoting cell intrinsic mechanisms to induce dormancy; preventing the engagement of dormant DTCs with their supportive niche in order to prevent their reactivation; targeting cell-intrinsic mechanisms mediating long-term survival of dormant DTCs; sensitizing dormant DTCs to chemotherapy treatments; and, inhibiting the immune evasion of dormant DTCs, leading to their demise. Various therapeutic approaches, some of which utilize drugs that are already approved, or have been tested in clinical trials and may be considered for repurposing, will be discussed. In addition, clinical evidence for the presence of dormant DTCs will be reviewed, along with potential prognostic biomarkers to enable the identification and stratification of patients who are at high risk of recurrence, and who could benefit from novel dormant DTCs targeting therapies. Finally, we will address the shortcomings of current trial designs for determining activity against dormant DTCs and provide novel approaches. |
| first_indexed | 2024-12-17T23:20:38Z |
| format | Article |
| id | doaj.art-8872efc4b1d643329129dfc4b8505032 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T23:20:38Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8872efc4b1d643329129dfc4b85050322022-12-21T21:28:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.659963659963Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor CellsScott Sauer0Damon R. Reed1Damon R. Reed2Damon R. Reed3Michael Ihnat4Robert E. Hurst5David Warshawsky6Dalit Barkan7Vuja De Sciences Inc., Hoboken, NJ, United StatesDepartment of Individualized Cancer Management, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United StatesCancer Biology and Evolution Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United StatesAdolescent and Young Adult Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United StatesDepartment of Pharmaceutical Sciences, College of Pharmacy, Oklahoma University Health Sciences Center, Oklahoma City, OK, United StatesVuja De Sciences Inc., Hoboken, NJ, United StatesVuja De Sciences Inc., Hoboken, NJ, United StatesDepartment of Human Biology and Medical Sciences, University of Haifa, Haifa, IsraelCancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents strategies to target dormant quiescent DTCs that reside at secondary sites. These strategies aim to prevent recurrence by maintaining dormant DTCs at bay, or eradicating them. Various approaches are presented, including: reinforcing the niche where dormant DTCs reside in order to keep dormant DTCs at bay; promoting cell intrinsic mechanisms to induce dormancy; preventing the engagement of dormant DTCs with their supportive niche in order to prevent their reactivation; targeting cell-intrinsic mechanisms mediating long-term survival of dormant DTCs; sensitizing dormant DTCs to chemotherapy treatments; and, inhibiting the immune evasion of dormant DTCs, leading to their demise. Various therapeutic approaches, some of which utilize drugs that are already approved, or have been tested in clinical trials and may be considered for repurposing, will be discussed. In addition, clinical evidence for the presence of dormant DTCs will be reviewed, along with potential prognostic biomarkers to enable the identification and stratification of patients who are at high risk of recurrence, and who could benefit from novel dormant DTCs targeting therapies. Finally, we will address the shortcomings of current trial designs for determining activity against dormant DTCs and provide novel approaches.https://www.frontiersin.org/articles/10.3389/fonc.2021.659963/fulltumor dormancymetastasisdisseminated tumor cellscancer recurrencetumor microenvironmentimmune evasion and clinical trials |
| spellingShingle | Scott Sauer Damon R. Reed Damon R. Reed Damon R. Reed Michael Ihnat Robert E. Hurst David Warshawsky Dalit Barkan Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells Frontiers in Oncology tumor dormancy metastasis disseminated tumor cells cancer recurrence tumor microenvironment immune evasion and clinical trials |
| title | Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells |
| title_full | Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells |
| title_fullStr | Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells |
| title_full_unstemmed | Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells |
| title_short | Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells |
| title_sort | innovative approaches in the battle against cancer recurrence novel strategies to combat dormant disseminated tumor cells |
| topic | tumor dormancy metastasis disseminated tumor cells cancer recurrence tumor microenvironment immune evasion and clinical trials |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.659963/full |
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