{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:19:32Z","timestamp":1787552372529,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["113-2320-B-037-003-MY2"],"award-info":[{"award-number":["113-2320-B-037-003-MY2"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["114-2320-B-037-019"],"award-info":[{"award-number":["114-2320-B-037-019"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["KMU-Q114007"],"award-info":[{"award-number":["KMU-Q114007"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet their efficacy remains limited by tumor resistance, immune-related adverse events, and poor response in microsatellite stable colorectal cancer (CRC). To address these challenges, dual monoamine oxidase A (MAO-A) and heat shock protein 90 (HSP90) inhibitors, MPT1B098 and MPT1B099, were developed and evaluated for their therapeutic potential and immune-modulatory efficacy in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human and murine CRC cell lines were treated with MPT1B098 and MPT1B099 to assess their effects in cytotoxicity, cell migration, apoptosis, cell cycle arrest, and cell-surface PD-L1 expression. Western blotting was performed to evaluate key apoptotic and EMT-related markers. In vivo therapeutic efficacy and safety were evaluated using CT26 and MC38 subcutaneous syngeneic tumor models in BALB\/c and C57BL\/6 mice treated with MPT1B098, MPT1B099, and\/or anti-PD1 antibodies. Tumor infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and tissue histopathology were evaluated by immunohistochemistry and H&amp;amp;E staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vitro, MPT1B098 and MPT1B099 exhibited potent cytotoxicity against human and murine CRC cell lines with sub-micromolar IC\n                      <jats:sub>50<\/jats:sub>\n                      values, effectively inhibiting cell growth and migration while inducing apoptosis. Both compounds decreased cell-surface PD-L1 expression and modulated key apoptotic and EMT markers on Western blot. In vivo, both compounds were well tolerated at 10 mg\/kg and significantly suppressed tumor growth in microsatellite instable and stable models. Notably, anti-PD1 monotherapy was effective only in MSI models, whereas MPT1B098 and MPT1B099 showed efficacy in both MSI and MSS tumors, with combination therapy producing a modest synergistic effect. Immunohistochemistry revealed increased CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration following treatment, particularly with MPT1B099 in combination with anti-PD1 antibodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings highlight the dual anti-tumor and immune-modulatory properties of MPT1B098 and MPT1B099, mediated in part through PD-L1 downregulation and enhanced intratumoral T cell infiltration. Dual targeting of MAO-A and HSP90 represents a promising novel strategy to overcome immunotherapy resistance in MSS CRC and enhance the therapeutic efficacy of immune checkpoint blockade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1866411","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:31:03Z","timestamp":1787549463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual MAO A and HSP90 inhibitors enhance anti-PD-1 therapy and suppress colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui-Ju","family":"Tseng","sequence":"first","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Lin","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University","place":["Taipei, Taiwan"]},{"name":"TMU Research Center of Urology and Kidney, Taipei Medical University","place":["Taipei, Taiwan"]},{"name":"Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suddhasatwa","family":"Banerjee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Ping","family":"Liou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University","place":["Taipei, Taiwan"]},{"name":"TMU Research Center for Drug Discovery, Taipei Medical University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","first-page":"9","article-title":"Treating with checkpoint inhibitors-figure $1 million per patient","volume":"8","author":"Andrews","year":"2015","journal-title":"Am. 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