{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:55:12Z","timestamp":1790603712871,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"54","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFC3408701"],"award-info":[{"award-number":["2025YFC3408701"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22177103"],"award-info":[{"award-number":["22177103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22577121"],"award-info":[{"award-number":["22577121"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Breast cancer remains one of the most prevalent malignancies among women, and taxane\u2010based chemotherapies such as paclitaxel and docetaxel are central to standard treatment regimens. However, drug resistance in breast cancer limits therapeutic efficacy and contributes to recurrence and metastasis. Identifying resistance\u2010associated molecular targets is therefore critical for advancing treatment strategies. To investigate paclitaxel resistance, we designed and synthesized four paclitaxel\u2010derived probes. Among these, PTX\u20104, constructed via a stable C\u2500C bond linkage, exhibited superior efficiency. Using a chemoproteomic approach, we systematically profiled paclitaxel\u2010binding proteins in parental and resistant breast cancer cells. This strategy successfully identified AKT2, an unrecognized paclitaxel\u2010interacting protein in paclitaxel\u2010resistant breast cancer. Functional validation demonstrated that AKT2 is a direct target of paclitaxel in paclitaxel\u2010resistant cells. Knockdown and pharmacological inhibition of AKT2 restored the sensitivity of paclitaxel\u2010resistant cells to paclitaxel. These findings establish AKT2 as a key mediator of paclitaxel resistance in breast cancer. Targeting AKT2 may offer a promising therapeutic strategy to overcome resistance and improve the clinical efficacy of taxane\u2010based chemotherapy. This study highlights the advantage of C\u2500C bond\u2010linked, pharmacologically active probes for chemoproteomic profiling of drug targets.<\/jats:p>","DOI":"10.1002\/advs.202520089","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:30:07Z","timestamp":1785447007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemoproteomic Identification of AKT2 as a Paclitaxel\u2010Binding Protein via C\u2500C Bond\u2010Linked Probe PTX\u20104 in Paclitaxel\u2010Resistant Breast Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6433-6528","authenticated-orcid":false,"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Surgery Affiliated Jinhua Hospital Zhejiang University School of Medicine  Jinhua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxiu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery Affiliated Jinhua Hospital Zhejiang University School of Medicine  Jinhua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Surgery Affiliated Jinhua Hospital Zhejiang University School of Medicine  Jinhua China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-0657","authenticated-orcid":false,"given":"Yi","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases Biomedical Engineering Facility of National Infrastructures For Translational Medicine Institute of Clinical Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0761-9434","authenticated-orcid":false,"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Green Chemical Synthesis and Conversion  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.19323"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010025\u201003734\u20103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1080684"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010025\u201000352\u2010w"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010018\u20100005\u20108"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101358"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.10.032"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119875"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1317"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010023\u201002879\u20108"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116609"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.101304.124125"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c03377"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01989"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010023\u201001409\u20105"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21880"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000508675"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010025\u201002422\u2010y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010022\u201000984\u20106"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.7314\/apjcp.2013.14.106135"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25020247"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00692"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7754\/clin.lab.2025.250547"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010024\u201000782\u20105"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.06.021"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.06.002"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010016\u20102598\u20101"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44244"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081058"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673327425240815065221"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010025\u201001059\u20101"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202520089","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202520089","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202520089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:58:47Z","timestamp":1790600327000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202520089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":32,"journal-issue":{"issue":"54","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.202520089"],"URL":"https:\/\/doi.org\/10.1002\/advs.202520089","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"assertion":[{"value":"2025-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e20089"}}