{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:06:44Z","timestamp":1789376804870,"version":"build-2803163510"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breast cancer is the most prevalent malignancy in women, and its complex tumor microenvironment (TME) characterized by immunosuppression, aberrant angiogenesis and stromal fibrosis is a critical cause of therapeutic failure. Traditional Chinese Medicine (TCM) herb pairs, with multi-target, multi-component and multi-dimensional modes of action, show unique advantages in modulating the breast cancer TME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Core findings<\/jats:title>\n                    <jats:p>\n                      This study systematically reviewed the regulatory mechanisms of 20 core anti-breast cancer herb pairs on the TME. Heat-clearing and detoxifying herb pairs (e.g.,\n                      <jats:italic>Hedyotis diffusa-Scutellaria barbata<\/jats:italic>\n                      ) principally reshape the immune microenvironment by activating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and promoting M2-to-M1 polarization of tumor-associated macrophages (TAMs). Blood-activating and stasis-resolving herb pairs (e.g.,\n                      <jats:italic>Sparganium stoloniferum-Curcuma zedoaria<\/jats:italic>\n                      ) inhibit tumor angiogenesis via targeting VEGF\/VEGFR2 and ITGA5\/CCN1 pathways. Qi-tonifying and pathogen-eliminating herb pairs (e.g.,\n                      <jats:italic>Astragalus membranaceus-C. zedoaria<\/jats:italic>\n                      ) ameliorate stromal fibrosis by suppressing cancer-associated fibroblast (CAF) activation and modulating the TGF-\u03b2\/Smad pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TCM herb pairs have substantial value in systematically remodeling the breast cancer TME and advancing integrative oncology. Nano-enabled delivery systems serve as a critical technical solution to overcome the intrinsic pharmacokinetic defects of herbal bioactive components and accelerate their clinical translation. The clinical translation pathway based on \u201csyndrome differentiation-guided herb pair selection\u2013precision TME modulation\u2013synergistic efficacy enhancement\u201d is expected to provide more precise, safe and effective therapeutic options for breast cancer patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1877992","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:46:29Z","timestamp":1789375589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TCM herb pairs regulate breast cancer TME heterogeneous mechanisms in immune, vascular, and stromal compartments"],"prefix":"10.3389","volume":"17","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Feng","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Fan","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Ding","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Min","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Dai","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Lei","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University Cancer Center Gansu Hospital","place":["Lanzhou, Gansu, China"]},{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shen","sequence":"additional","affiliation":[{"name":"Gansu Academy of Medical Sciences","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","first-page":"906","article-title":"Research progress of traditional Chinese medicine and its active components targeting tumor microenvironment","volume":"37","author":"Bai","year":"2022","journal-title":"China J. 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