Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel
Taxanes and CDK4/6 inhibitors (CDK4/6i) are two families of successful anti-mitotic drugs used in the treatment of solid tumors. Paclitaxel, representing taxane compounds, has been used either alone or in combination with other agents (commonly carboplatin/cisplatin) in the treatment of many solid t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.907520/full |
| _version_ | 1797995306407690240 |
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| author | Elizabeth R. Smith Elizabeth R. Smith Marilyn Huang Marilyn Huang Matthew P. Schlumbrecht Matthew P. Schlumbrecht Sophia H.L. George Sophia H.L. George Xiang-Xi Xu Xiang-Xi Xu |
| author_facet | Elizabeth R. Smith Elizabeth R. Smith Marilyn Huang Marilyn Huang Matthew P. Schlumbrecht Matthew P. Schlumbrecht Sophia H.L. George Sophia H.L. George Xiang-Xi Xu Xiang-Xi Xu |
| author_sort | Elizabeth R. Smith |
| collection | DOAJ |
| description | Taxanes and CDK4/6 inhibitors (CDK4/6i) are two families of successful anti-mitotic drugs used in the treatment of solid tumors. Paclitaxel, representing taxane compounds, has been used either alone or in combination with other agents (commonly carboplatin/cisplatin) in the treatment of many solid tumors including ovarian, breast, lung, prostate cancers, and Kaposi’s sarcoma. Paclitaxel has been routinely prescribed in cancer treatment since the 1990s, and its prominent role is unlikely to be replaced in the foreseeable future. Paclitaxel and other taxanes work by binding to and stabilizing microtubules, causing mitotic arrest, aberrant mitosis, and cell death. CDK4/6i (palbociclib, ribociclib, abemaciclib) are relatively new cell cycle inhibitors that have been found to be effective in breast cancer treatment, and are currently being developed in other solid tumors. CDK4/6i blocks cell cycle progression at the G1 phase, resulting in cell death by mechanisms not yet fully elucidated. At first glance, paclitaxel and CDK4/6i are unlikely synergistic agents as both are cell cycle inhibitors that work at different phases of the cell cycle, and few clinical trials have yet considered adding CDK4/6i to existing paclitaxel chemotherapy. However, recent findings suggest the importance of a non-mitotic mechanism of paclitaxel in cancer cell death and pre-clinical data support rationale for a strategic paclitaxel and CDK4/6i combination. In mouse tumor model studies, drug sequencing resulted in differential efficacy, indicating complex biological interactions of the two drugs. This article reviews the rationales of combining paclitaxel with CDK4/6i as a potential therapeutic option in recurrent ovarian cancer. |
| first_indexed | 2024-04-11T09:59:39Z |
| format | Article |
| id | doaj.art-8368702b2245426eb661270bc34a9171 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T09:59:39Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8368702b2245426eb661270bc34a91712022-12-22T04:30:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.907520907520Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxelElizabeth R. Smith0Elizabeth R. Smith1Marilyn Huang2Marilyn Huang3Matthew P. Schlumbrecht4Matthew P. Schlumbrecht5Sophia H.L. George6Sophia H.L. George7Xiang-Xi Xu8Xiang-Xi Xu9Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Obstetrics, Gynecology and Reproductive Science, University of Miami Miller School of Medicine, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Obstetrics, Gynecology and Reproductive Science, University of Miami Miller School of Medicine, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Obstetrics, Gynecology and Reproductive Science, University of Miami Miller School of Medicine, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Obstetrics, Gynecology and Reproductive Science, University of Miami Miller School of Medicine, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, United StatesTaxanes and CDK4/6 inhibitors (CDK4/6i) are two families of successful anti-mitotic drugs used in the treatment of solid tumors. Paclitaxel, representing taxane compounds, has been used either alone or in combination with other agents (commonly carboplatin/cisplatin) in the treatment of many solid tumors including ovarian, breast, lung, prostate cancers, and Kaposi’s sarcoma. Paclitaxel has been routinely prescribed in cancer treatment since the 1990s, and its prominent role is unlikely to be replaced in the foreseeable future. Paclitaxel and other taxanes work by binding to and stabilizing microtubules, causing mitotic arrest, aberrant mitosis, and cell death. CDK4/6i (palbociclib, ribociclib, abemaciclib) are relatively new cell cycle inhibitors that have been found to be effective in breast cancer treatment, and are currently being developed in other solid tumors. CDK4/6i blocks cell cycle progression at the G1 phase, resulting in cell death by mechanisms not yet fully elucidated. At first glance, paclitaxel and CDK4/6i are unlikely synergistic agents as both are cell cycle inhibitors that work at different phases of the cell cycle, and few clinical trials have yet considered adding CDK4/6i to existing paclitaxel chemotherapy. However, recent findings suggest the importance of a non-mitotic mechanism of paclitaxel in cancer cell death and pre-clinical data support rationale for a strategic paclitaxel and CDK4/6i combination. In mouse tumor model studies, drug sequencing resulted in differential efficacy, indicating complex biological interactions of the two drugs. This article reviews the rationales of combining paclitaxel with CDK4/6i as a potential therapeutic option in recurrent ovarian cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.907520/fullchemotherapytaxanes/taxol/paclitaxelmicrotubulesmitosisnuclear envelopemicronuclei |
| spellingShingle | Elizabeth R. Smith Elizabeth R. Smith Marilyn Huang Marilyn Huang Matthew P. Schlumbrecht Matthew P. Schlumbrecht Sophia H.L. George Sophia H.L. George Xiang-Xi Xu Xiang-Xi Xu Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel Frontiers in Oncology chemotherapy taxanes/taxol/paclitaxel microtubules mitosis nuclear envelope micronuclei |
| title | Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel |
| title_full | Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel |
| title_fullStr | Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel |
| title_full_unstemmed | Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel |
| title_short | Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy — non-mitotic mechanisms of paclitaxel |
| title_sort | rationale for combination of paclitaxel and cdk4 6 inhibitor in ovarian cancer therapy non mitotic mechanisms of paclitaxel |
| topic | chemotherapy taxanes/taxol/paclitaxel microtubules mitosis nuclear envelope micronuclei |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.907520/full |
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