{"id":349,"date":"2026-09-21T08:03:29","date_gmt":"2026-09-21T08:03:29","guid":{"rendered":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/?page_id=349"},"modified":"2026-09-21T09:41:36","modified_gmt":"2026-09-21T09:41:36","slug":"nepc-en-translation","status":"publish","type":"page","link":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/en\/research-themes\/nepc-en-translation\/","title":{"rendered":"NEPC"},"content":{"rendered":"\n
\n
\n

Neuroendocrine Prostate Cancer (NEPC)<\/h3>\n\n\n\n

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer associated with treatment resistance and poor clinical outcomes.<\/p>\n\n\n\n

In addition to tumors that exhibit neuroendocrine features at initial diagnosis, treatment-emergent NEPC (t-NEPC)<\/strong> can develop during the course of treatment for advanced prostate cancer, particularly following androgen receptor (AR)-targeted therapies.<\/p>\n\n\n\n

Our research focuses on lineage plasticity<\/strong>, through which prostate cancer cells alter their cellular identity during the acquisition of treatment resistance, as well as on the tumor microenvironment<\/strong> that may promote and sustain this transition.<\/p>\n<\/div>\n\n\n\n

\n
\"\"<\/figure>\n\n\n\n

Watanabe R, Haffner M, Nelson P et al. Urol. Oncol. 2026<\/p>\n<\/div>\n<\/div>\n\n\n\n

<\/p>\n\n\n\n

\n
\n

How does prostate cancer evolve into NEPC?<\/h3>\n\n\n\n

We compare prostate adenocarcinoma before treatment with NEPC that emerges after therapy in the same patients and perform high-resolution spatial transcriptomic analyses.<\/p>\n\n\n\n

By analyzing not only tumor cells but also surrounding stromal and immune cells, we aim to characterize changes in gene expression and tumor\u2013microenvironment interactions associated with the transition to NEPC.<\/p>\n\n\n\n

In particular, we investigate SASP, inflammation, TGF-\u03b2, NF-\u03baB, and interferon signaling<\/strong> to understand the microenvironmental factors that may contribute to treatment resistance and neuroendocrine differentiation.<\/p>\n<\/div>\n\n\n\n

\n
\n
\n
\"\"<\/figure>\n<\/div>\n\n\n\n
\n
\"\"<\/figure>\n<\/div>\n<\/div>\n\n\n\n

Watanabe et al. Int J Mol Sci 2023<\/p>\n\n\n\n

<\/p>\n<\/div>\n<\/div>\n\n\n\n

\n
\n

Molecular Characterization of NEPC through a Nationwide Cohort<\/h3>\n\n\n\n

NEPC is a rare disease, making it difficult for any single institution to collect and analyze a sufficiently large number of cases.<\/p>\n\n\n\n

To address this challenge, we have established a nationwide multicenter cohort of NEPC<\/strong> in collaboration with institutions across Japan and are conducting RNA sequencing and spatial transcriptomic analyses.<\/p>\n\n\n\n

By characterizing the transition to NEPC at spatial resolution and validating these findings in the nationwide cohort, we aim to establish a molecular classification of NEPC, identify predictors of NEPC development, and discover novel therapeutic targets<\/strong>.<\/p>\n<\/div>\n\n\n\n

\n
\n
\n
\n
\n
\"\"<\/figure>\n<\/div>\n\n\n\n
\n
\"\"<\/figure>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n

<\/p>\n\n\n\n

Toward Prediction and Treatment of NEPC<\/h3>\n\n\n\n

Our ultimate goal is not simply to diagnose NEPC after it has developed, but to predict which prostate cancers are likely to progress to NEPC and intervene early in this process<\/strong>.<\/p>\n\n\n\n

We validate findings from patient-derived specimens using experimental models, including patient-derived xenografts (PDXs) and organoids<\/strong>, with the goal of translating these discoveries into new diagnostic and therapeutic strategies.<\/p>\n\n\n\n

<\/p>\n\n\n\n

Related Publications<\/h2>\n\n\n\n

Enzalutamide promotes an early plasticity-associated transcriptional state without terminal neuroendocrine differentiation in prostate cancer cells<\/strong>
Watanabe R, Chosei M, Arai H, Miura N, Kikugawa T, Saika T.
Front Oncol. 2026;16:1870253.<\/em>
PMID: 42568401<\/a><\/p>\n\n\n\n

Cellular plasticity and tumor ecosystem dynamics in prostate cancer: insights from single-cell and spatial transcriptomics<\/strong>
Watanabe R, Chu T, Miura N, Kikugawa T, Nelson PS, Saika T.
Am J Clin Exp Urol. 2026;14(3):64-85.<\/em>
PMID: 42488354<\/a><\/p>\n\n\n\n

Molecular pathology of rare histologic variants and treatment-resistant lineages of prostate cancer<\/strong>
Watanabe R, Miura N, Kikugawa T, Saika T, Haffner MC, Nelson PS.
Urol Oncol. 2026;44(4):110987.<\/em>
PMID: 41605126<\/a><\/p>\n\n\n\n

Paired-sample Analysis of ERG Expression and TMPRSS2-ERG Fusion in Treatment-induced Neuroendocrine Prostate Cancer<\/strong>
Watanabe R, Shigehisa R, Kawada T, Yamamoto S, Katayama S, Takamoto A, Nishimura K, Miura N, Araki M, Inoue K, Saika T; Chu-shikoku Japan Urological Consortium (CsJUC) Research Collaboration.
Anticancer Res. 2026;46(4):1929-1942.<\/em>
PMID: 41895744<\/a><\/p>\n\n\n\n

Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer<\/strong>
Watanabe R, Miura N, Kurata M, Kitazawa R, Kikugawa T, Saika T.
Int J Mol Sci. 2023;24(10):8955.<\/em>
PMID: 37240308<\/a><\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Neuroendocrine Prostate Cancer (NEPC) Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prosta […]<\/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-349","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\/349","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=349"}],"version-history":[{"count":3,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/349\/revisions"}],"predecessor-version":[{"id":352,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/349\/revisions\/352"}],"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=349"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}