{"id":362,"date":"2026-09-21T08:22:57","date_gmt":"2026-09-21T08:22:57","guid":{"rendered":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/?page_id=362"},"modified":"2026-09-21T09:43:04","modified_gmt":"2026-09-21T09:43:04","slug":"%ef%bd%8dhnpc","status":"publish","type":"page","link":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/en\/research-themes\/%ef%bd%8dhnpc\/","title":{"rendered":"\uff4dHNPC"},"content":{"rendered":"\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7387b849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<h3 class=\"wp-block-heading\">Metastatic Hormone-Na\u00efve Prostate Cancer (mHNPC)<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Metastatic hormone-na\u00efve prostate cancer (mHNPC)<\/strong> is prostate cancer that has spread to distant sites but remains sensitive to androgen deprivation therapy.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In recent years, treatment outcomes have improved through the early use of intensified hormonal therapy and chemotherapy. However, even among patients with mHNPC, <strong>treatment responses and subsequent clinical courses vary substantially<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Our research focuses on <strong>tumor heterogeneity that is already present before treatment begins<\/strong>.\u3002<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"312\" height=\"320\" src=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC1.png\" alt=\"\" class=\"wp-image-255\" srcset=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC1.png 312w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC1-293x300.png 293w\" sizes=\"auto, (max-width: 312px) 100vw, 312px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7387b849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<h3 class=\"wp-block-heading\">Distinct Cellular States Coexist within a Single Tumor<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">We perform <strong>single-cell RNA sequencing<\/strong> of treatment-na\u00efve mHNPC specimens to characterize the cellular composition of individual tumors at single-cell resolution.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Our analyses reveal that, even before treatment, tumors contain not only conventional <strong>Luminal\/AR-positive<\/strong> cancer cells but also distinct epithelial populations with <strong>Basal\/Stem-like and EMT\/stromal-like features<\/strong>.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"322\" src=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC2-1024x322.jpg\" alt=\"\" class=\"wp-image-256\" srcset=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC2-1024x322.jpg 1024w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC2-300x94.jpg 300w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC2-768x242.jpg 768w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC2-1536x484.jpg 1536w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC2.jpg 1880w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7387b849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<h3 class=\"wp-block-heading\">Pre-existing \u201cSeeds of Resistance\u201d before Treatment<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Tumors with basal-associated features show increased activity of <strong>stem-like, EMT, TGF-\u03b2, and p53-related programs<\/strong>, which are associated with treatment resistance and tumor progression.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In contrast, we did not identify a distinct neuroendocrine tumor-cell population in the treatment-na\u00efve mHNPC specimens analyzed.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">These findings suggest that prostate cancer may not become heterogeneous only after exposure to therapy. Instead, <strong>cellular states with the potential to contribute to future treatment resistance may already exist before treatment begins<\/strong>.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"290\" src=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC3-1024x290.jpg\" alt=\"\" class=\"wp-image-257\" srcset=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC3-1024x290.jpg 1024w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC3-300x85.jpg 300w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC3-768x218.jpg 768w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC3-1536x435.jpg 1536w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/\uff4dHNPC3.jpg 1880w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7387b849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<h3 class=\"wp-block-heading\">Looking Beyond Tumor Burden to \u201cTumor Biology\u201d<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Current treatment strategies for mHNPC are largely guided by clinical factors such as <strong>metastatic burden and risk classification<\/strong>. However, even among patients with similar clinical features, the cellular states that constitute their tumors may differ substantially.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Using single-cell approaches, we aim to characterize <strong>biological aggressiveness and potential treatment resistance before therapy begins<\/strong> and to develop biomarkers that can guide <strong>more individualized treatment selection for each patient<\/strong>.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"512\" src=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC4-1024x512.png\" alt=\"\" class=\"wp-image-258\" style=\"aspect-ratio:2.0000428485731425;width:663px;height:auto\" srcset=\"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC4-1024x512.png 1024w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC4-300x150.png 300w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC4-768x384.png 768w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC4-1536x768.png 1536w, https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-content\/uploads\/2026\/09\/mHNPC4.png 1774w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Related Publications<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Single-Cell Analysis Reveals Pre-Existing Basal-Associated Epithelial States in Metastatic Hormone-Na\u00efve Prostate Cancer<\/strong><br>Watanabe R, Chosei M, Sakaue T, Miura N, Kikugawa T, Saika T.<br><em>Int J Mol Sci. 2026 Jun 16;27(12):5405.<\/em><br><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42353123\/\" target=\"_blank\" rel=\"noopener\">PMID: 42353123<\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Enzalutamide promotes an early plasticity-associated transcriptional state without terminal neuroendocrine differentiation in prostate cancer cells<\/strong><br>Watanabe R, Chosei M, Arai H, Miura N, Kikugawa T, Saika T.<br><em>Front Oncol. 2026 Jul 24;16:1870253.<\/em><br><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42568401\/\" target=\"_blank\" rel=\"noopener\">PMID: 42568401<\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Cellular plasticity and tumor ecosystem dynamics in prostate cancer: insights from single-cell and spatial transcriptomics<\/strong><br>Watanabe R, Chu T, Miura N, Kikugawa T, Nelson PS, Saika T.<br><em>Am J Clin Exp Urol. 2026 Jun 15;14(3):64-85.<\/em><br><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42488354\/\" target=\"_blank\" rel=\"noopener\">PMID: 42488354<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Metastatic Hormone-Na\u00efve Prostate Cancer (mHNPC) Metastatic hormone-na\u00efve prostate cancer (mHNPC) is prostate  [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":376,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"sns_share_botton_hide":"","vkExUnit_sns_title":"","_vk_print_noindex":"","sitemap_hide":"","vkExUnit_sitemap":"","_veu_custom_css":"","veu_display_promotion_alert":"","_exclude_from_list_pages":"","vkexunit_cta_each_option":"","vkExUnit_childPageIndex":"","vkExUnit_pageList_ancestor":"","vkExUnit_contact_enable":"","_lightning_design_setting":{"layout":"col-one-no-subsection"},"footnotes":""},"class_list":["post-362","page","type-page","status-publish","hentry"],"veu_head_title_object":{"title":"","add_site_title":""},"_links":{"self":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/362","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/comments?post=362"}],"version-history":[{"count":2,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/362\/revisions"}],"predecessor-version":[{"id":364,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/362\/revisions\/364"}],"up":[{"embeddable":true,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/376"}],"wp:attachment":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/media?parent=362"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}