First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations
Tumors include a heterogeneous population, of which a small proportion includes drug-resistant cancer (stem) cells. In drug-sensitive cancer populations, first-line chemotherapy reduces tumor volume via apoptosis. However, it stimulates drug-resistant cancer populations and finally results in tumor...
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description | Tumors include a heterogeneous population, of which a small proportion includes drug-resistant cancer (stem) cells. In drug-sensitive cancer populations, first-line chemotherapy reduces tumor volume via apoptosis. However, it stimulates drug-resistant cancer populations and finally results in tumor recurrence. Recurrent tumors are unresponsive to chemotherapeutic drugs and are primarily drug-resistant cancers. Therefore, increased apoptosis in drug-resistant cancer cells in heterogeneous populations is important in first-line chemotherapeutic treatments. The overexpression of ABCB1 (or P-gp) on cell membranes is an important characteristic of drug-resistant cancer cells; therefore, first-line combination treatments with P-gp inhibitors could delay tumor recurrence. Low doses of bipolar drugs showed P-gp inhibitory activity, and their use as a combined therapy sensitized drug-resistant cancer cells. FDA-approved bipolar drugs have been used in clinics for a long period of time, and their toxicities are well reported. They can be easily applied as first-line combination treatments for targeting resistant cancer populations. To apply bipolar drugs faster in first-line combination treatments, knowledge of their complete information is crucial. This review discusses the use of low-dose bipolar drugs in sensitizing ABCB1-overexpressing, drug-resistant cancers. We believe that this review will contribute to facilitating first-line combination treatments with low-dose bipolar drugs for targeting drug-resistant cancer populations. In addition, our findings may aid further investigations into targeting drug-resistant cancer populations with low-dose bipolar drugs. |
doi_str_mv | 10.3390/ijms24098389 |
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In drug-sensitive cancer populations, first-line chemotherapy reduces tumor volume via apoptosis. However, it stimulates drug-resistant cancer populations and finally results in tumor recurrence. Recurrent tumors are unresponsive to chemotherapeutic drugs and are primarily drug-resistant cancers. Therefore, increased apoptosis in drug-resistant cancer cells in heterogeneous populations is important in first-line chemotherapeutic treatments. The overexpression of ABCB1 (or P-gp) on cell membranes is an important characteristic of drug-resistant cancer cells; therefore, first-line combination treatments with P-gp inhibitors could delay tumor recurrence. Low doses of bipolar drugs showed P-gp inhibitory activity, and their use as a combined therapy sensitized drug-resistant cancer cells. FDA-approved bipolar drugs have been used in clinics for a long period of time, and their toxicities are well reported. They can be easily applied as first-line combination treatments for targeting resistant cancer populations. To apply bipolar drugs faster in first-line combination treatments, knowledge of their complete information is crucial. This review discusses the use of low-dose bipolar drugs in sensitizing ABCB1-overexpressing, drug-resistant cancers. We believe that this review will contribute to facilitating first-line combination treatments with low-dose bipolar drugs for targeting drug-resistant cancer populations. In addition, our findings may aid further investigations into targeting drug-resistant cancer populations with low-dose bipolar drugs.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24098389</identifier><identifier>PMID: 37176096</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Apoptosis ; ATP Binding Cassette Transporter, Subfamily B - genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Blood-brain barrier ; Breast cancer ; Cancer ; Cancer therapies ; Cell cycle ; Cell Line, Tumor ; Cell membranes ; Chemotherapy ; Clinical trials ; Cytotoxicity ; Dopamine ; Dosage and administration ; Drug approval ; Drug delivery ; Drug dosages ; Drug resistance ; Drug Resistance, Neoplasm ; Drug therapy ; Drugs ; Humans ; Iloperidone ; Kinases ; Loxapine ; Neoplasm Recurrence, Local ; Populations ; Psychotropic drugs ; Radiation ; Review ; Thioridazine ; Tumors ; Vincristine</subject><ispartof>International journal of molecular sciences, 2023-05, Vol.24 (9), p.8389</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c437t-c76dec6b514f8348f1134d54539dc72eb39f81fee633695fe89c452562a5c7d73</cites><orcidid>0000-0002-9301-6313 ; 0000-0001-7657-3970</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179254/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179254/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37176096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoon, Sungpil</creatorcontrib><creatorcontrib>Kim, Hyung Sik</creatorcontrib><title>First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Tumors include a heterogeneous population, of which a small proportion includes drug-resistant cancer (stem) cells. In drug-sensitive cancer populations, first-line chemotherapy reduces tumor volume via apoptosis. However, it stimulates drug-resistant cancer populations and finally results in tumor recurrence. Recurrent tumors are unresponsive to chemotherapeutic drugs and are primarily drug-resistant cancers. Therefore, increased apoptosis in drug-resistant cancer cells in heterogeneous populations is important in first-line chemotherapeutic treatments. The overexpression of ABCB1 (or P-gp) on cell membranes is an important characteristic of drug-resistant cancer cells; therefore, first-line combination treatments with P-gp inhibitors could delay tumor recurrence. Low doses of bipolar drugs showed P-gp inhibitory activity, and their use as a combined therapy sensitized drug-resistant cancer cells. FDA-approved bipolar drugs have been used in clinics for a long period of time, and their toxicities are well reported. They can be easily applied as first-line combination treatments for targeting resistant cancer populations. To apply bipolar drugs faster in first-line combination treatments, knowledge of their complete information is crucial. This review discusses the use of low-dose bipolar drugs in sensitizing ABCB1-overexpressing, drug-resistant cancers. We believe that this review will contribute to facilitating first-line combination treatments with low-dose bipolar drugs for targeting drug-resistant cancer populations. In addition, our findings may aid further investigations into targeting drug-resistant cancer populations with low-dose bipolar drugs.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>ATP Binding Cassette Transporter, Subfamily B - genetics</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Blood-brain barrier</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell membranes</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Cytotoxicity</subject><subject>Dopamine</subject><subject>Dosage and administration</subject><subject>Drug approval</subject><subject>Drug delivery</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Humans</subject><subject>Iloperidone</subject><subject>Kinases</subject><subject>Loxapine</subject><subject>Neoplasm Recurrence, Local</subject><subject>Populations</subject><subject>Psychotropic drugs</subject><subject>Radiation</subject><subject>Review</subject><subject>Thioridazine</subject><subject>Tumors</subject><subject>Vincristine</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkktv1DAUhSMEoqWwY40isWFBit-PFZqZUkAaqQiVteVxbqYeJXawkw78e5K2jKYIeWHL97vn-linKF5jdE6pRh_8rsuEIa2o0k-KU8wIqRAS8unR-aR4kfMOIUIJ18-LEyqxFEiL02J_6VMeqrUPUK5it_HBDj6G8jqBHToIQ7n3w025jvvqImYol76PrU3lRRq3uWxiKhfL1RJXV7eQ4FefIGcftnfl6jtknwc7aaxscJDKb7Ef2zv9_LJ41tg2w6uH_az4cfnpevWlWl99_rparCvHqBwqJ0UNTmw4Zo2iTDUYU1ZzxqmunSSwobpRuAEQlArNG1DaMU64IJY7WUt6Vny81-3HTQe1mxwl25o--c6m3yZabx5Xgr8x23hrMMJSE84mhXcPCin-HCEPpvPZQdvaAHHMhihMOVeCzcPe_oPu4pjC5G-miMBKT-8_UFvbgvGhidNgN4uaheSEESrUTJ3_h5pWDZ13MUDjp_tHDe_vG1yKOSdoDiYxMnNSzHFSJvzN8ccc4L_RoH8A6jy5Og</recordid><startdate>20230507</startdate><enddate>20230507</enddate><creator>Yoon, Sungpil</creator><creator>Kim, Hyung Sik</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9301-6313</orcidid><orcidid>https://orcid.org/0000-0001-7657-3970</orcidid></search><sort><creationdate>20230507</creationdate><title>First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations</title><author>Yoon, Sungpil ; Kim, Hyung Sik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-c76dec6b514f8348f1134d54539dc72eb39f81fee633695fe89c452562a5c7d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>ATP Binding Cassette Transporter, Subfamily B - genetics</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Blood-brain barrier</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell membranes</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Cytotoxicity</topic><topic>Dopamine</topic><topic>Dosage and administration</topic><topic>Drug approval</topic><topic>Drug delivery</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Drug therapy</topic><topic>Drugs</topic><topic>Humans</topic><topic>Iloperidone</topic><topic>Kinases</topic><topic>Loxapine</topic><topic>Neoplasm Recurrence, Local</topic><topic>Populations</topic><topic>Psychotropic drugs</topic><topic>Radiation</topic><topic>Review</topic><topic>Thioridazine</topic><topic>Tumors</topic><topic>Vincristine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoon, Sungpil</creatorcontrib><creatorcontrib>Kim, Hyung Sik</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoon, Sungpil</au><au>Kim, Hyung Sik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-05-07</date><risdate>2023</risdate><volume>24</volume><issue>9</issue><spage>8389</spage><pages>8389-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Tumors include a heterogeneous population, of which a small proportion includes drug-resistant cancer (stem) cells. In drug-sensitive cancer populations, first-line chemotherapy reduces tumor volume via apoptosis. However, it stimulates drug-resistant cancer populations and finally results in tumor recurrence. Recurrent tumors are unresponsive to chemotherapeutic drugs and are primarily drug-resistant cancers. Therefore, increased apoptosis in drug-resistant cancer cells in heterogeneous populations is important in first-line chemotherapeutic treatments. The overexpression of ABCB1 (or P-gp) on cell membranes is an important characteristic of drug-resistant cancer cells; therefore, first-line combination treatments with P-gp inhibitors could delay tumor recurrence. Low doses of bipolar drugs showed P-gp inhibitory activity, and their use as a combined therapy sensitized drug-resistant cancer cells. FDA-approved bipolar drugs have been used in clinics for a long period of time, and their toxicities are well reported. They can be easily applied as first-line combination treatments for targeting resistant cancer populations. To apply bipolar drugs faster in first-line combination treatments, knowledge of their complete information is crucial. This review discusses the use of low-dose bipolar drugs in sensitizing ABCB1-overexpressing, drug-resistant cancers. We believe that this review will contribute to facilitating first-line combination treatments with low-dose bipolar drugs for targeting drug-resistant cancer populations. In addition, our findings may aid further investigations into targeting drug-resistant cancer populations with low-dose bipolar drugs.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37176096</pmid><doi>10.3390/ijms24098389</doi><orcidid>https://orcid.org/0000-0002-9301-6313</orcidid><orcidid>https://orcid.org/0000-0001-7657-3970</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis ATP Binding Cassette Transporter, Subfamily B - genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Blood-brain barrier Breast cancer Cancer Cancer therapies Cell cycle Cell Line, Tumor Cell membranes Chemotherapy Clinical trials Cytotoxicity Dopamine Dosage and administration Drug approval Drug delivery Drug dosages Drug resistance Drug Resistance, Neoplasm Drug therapy Drugs Humans Iloperidone Kinases Loxapine Neoplasm Recurrence, Local Populations Psychotropic drugs Radiation Review Thioridazine Tumors Vincristine |
title | First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations |
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