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This review highlights ABCB1 (P-gp) overexpression as a key resistance feature and evaluates low-dose bipolar drugs that inhibit P-gp and sensitize resistant cells, supporting faster, clinically feasible first-line combination strategies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/first-line-combination-treatment-with-low-dose-bipolar-drugs-for-abcb1-overexpressing-drug-resistant-cancer-populations/383626/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/first-line-combination-treatment-with-low-dose-bipolar-drugs-for-abcb1-overexpressing-drug-resistant-cancer-populations/383626.png","ImageObject",300,407,{"name":42,"@type":43},"Miles","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why do first-line chemotherapies often lead to tumor recurrence?","Question",{"text":63,"@type":64},"They can trigger apoptosis in drug-sensitive populations but also stimulate drug-resistant cancer populations. This shift increases recurrence because recurrent tumors are primarily drug-resistant and less responsive to chemotherapy.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role does ABCB1 (P-gp) play in drug resistance?",{"text":68,"@type":64},"ABCB1/P-gp overexpression on cancer cell membranes actively pumps chemotherapeutic drugs out of cells. This reduces intracellular toxicity and supports the survival and growth of resistant tumors.",{"name":70,"@type":61,"acceptedAnswer":71},"How do low-dose bipolar drugs contribute to the proposed combination treatment?",{"text":72,"@type":64},"Low doses of bipolar drugs show P-gp inhibitory activity and can sensitize ABCB1-overexpressing drug-resistant cancer cells. The review argues that this enables more effective first-line combination treatment to delay relapse and reduce resistant populations.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},383626,1790555092,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Review  \nFirst-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations  \nSungpil Yoon * and Hyung Sik Kim *  \nCitation: Yoon, S.; Kim, H.S.  \nFirst-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing  \nDrug-Resistant Cancer Populations. Int. J. Mol. Sci. 2023, 24, 8389 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24098389  \nAcademic Editor: Cristina Marzano  \nReceived: 31 March 2023  \nRevised: 25 April 2023  \nAccepted: 5 May 2023  \nPublished: 7 May 2023  \nCopyright: © 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nSchool of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea * Correspondence: [syoon88@gmail.com](syoon88@gmail.com) (S.Y.); [hkims@skku.edu](hkims@skku.edu) (H.S.K.); Tel.: +82-1055024893 (S.Y.);  \nFax: +82-312928800 (S.Y.)  \nAbstract: Tumors include a heterogeneous population, of which a small proportion includes drugresistant 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.  \nKeywords: bipolar drugs; heterogeneous resistant cancer population; first-line combination treatment; ABCB1 (or P-gp) overexpression  \n1. Introduction  \nTumors associated with poor survival comprise high-grade, metastatic, advanced, and aggressive cancers because they are difficult to remove with surgery and can recur in a short time or eventually with the use of currently available chemotherapeutic drugs. These tumors include ovarian cancer, pancreatic cancer, lung cancer, glioma, and triple-negative breast cancer (TNBC) . Therefore, other treatment strategies are needed to remove the tumor or delay tumor recurrence. Tumors comprise a heterogeneous population that mainly contains chemotherapeutic drug-sensitive cancer cells. However, a small proportion of tumors are composed of multidrug-resistance (MDR) cancer cells, which include cancer stem cells (CSCs) [1,2] .  \nA critical mechanism for evading chemotherapeutic toxicity is the overexpression of ABCB1 protein or P-glycoprotein (P-gp) on their membranes and the active pumping of chemotherapeutic drugs as substrates from cancer ce","cbCaivqRtlrKxlLE","https://ap.wps.com/l/cbCaivqRtlrKxlLE","pdf",1018766,13,"English","# Abstract\n# Keywords\n# 1. Introduction\n## Tumor heterogeneity and recurrence risk\n## ABCB1/P-gp-mediated multidrug resistance\n## Rationale for P-gp inhibitor combination strategies\n# Figure 1. Co-treatment effects on ABCB1-overexpressing resistant cancers","[{\"question\":\"Why do first-line chemotherapies often lead to tumor recurrence?\",\"answer\":\"They can trigger apoptosis in drug-sensitive populations but also stimulate drug-resistant cancer populations. This shift increases recurrence because recurrent tumors are primarily drug-resistant and less responsive to chemotherapy.\"},{\"question\":\"What role does ABCB1 (P-gp) play in drug resistance?\",\"answer\":\"ABCB1/P-gp overexpression on cancer cell membranes actively pumps chemotherapeutic drugs out of cells. This reduces intracellular toxicity and supports the survival and growth of resistant tumors.\"},{\"question\":\"How do low-dose bipolar drugs contribute to the proposed combination treatment?\",\"answer\":\"Low doses of bipolar drugs show P-gp inhibitory activity and can sensitize ABCB1-overexpressing drug-resistant cancer cells. The review argues that this enables more effective first-line combination treatment to delay relapse and reduce resistant populations.\"}]","First-Line Combination Treatment with Low-Dose Bipolar Drugs for ABCB1-Overexpressing Drug-Resistant Cancer Populations | PDF",1790258460,33]