{"id":731,"date":"2026-10-12T00:30:31","date_gmt":"2026-10-11T15:30:31","guid":{"rendered":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/?page_id=731"},"modified":"2026-10-12T00:35:58","modified_gmt":"2026-10-11T15:35:58","slug":"nepc-2","status":"publish","type":"page","link":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/en\/research-themes\/nepc-2\/","title":{"rendered":"NEPC"},"content":{"rendered":"\n
\n
\n

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

Neuroendocrine prostate cancer (NEPC) is a highly treatment-resistant form of prostate cancer associated with a poor prognosis.<\/p>\n\n\n\n

NEPC can arise de novo, exhibiting neuroendocrine features at initial diagnosis, or develop during treatment for advanced prostate cancer, particularly following androgen deprivation therapy and other androgen receptor-targeted treatments. The latter is referred to as treatment-emergent NEPC (t-NEPC).<\/p>\n\n\n\n

Our research focuses on lineage plasticity, through which prostate cancer cells acquire treatment resistance and undergo phenotypic changes, as well as the tumor microenvironment that surrounds and potentially influences this process.<\/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 Transform into NEPC?<\/h3>\n\n\n\n

We are conducting high-resolution spatial transcriptomic analyses of paired tumor specimens collected from the same patients before treatment, when the tumors exhibited conventional prostate adenocarcinoma features, and after progression to NEPC.<\/p>\n\n\n\n

By examining not only tumor cells but also surrounding stromal and immune cells, we aim to characterize the changes in gene expression associated with neuroendocrine differentiation and elucidate their interactions with the tumor microenvironment.<\/p>\n\n\n\n

We are particularly interested in senescence-associated secretory phenotype (SASP), inflammation, TGF-\u03b2, NF-\u03baB, and interferon (IFN) signaling pathways, and their potential roles in promoting 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

Understanding the Molecular Pathogenesis of NEPC Through a Nationwide Cohort<\/h3>\n\n\n\n

NEPC is a relatively rare disease, making it challenging for individual institutions to collect sufficient numbers of cases for comprehensive molecular analyses.<\/p>\n\n\n\n

To address this limitation, we are collaborating with medical institutions across Japan to establish a nationwide NEPC cohort and conduct RNA sequencing and spatial transcriptomic analyses.<\/p>\n\n\n\n

By integrating detailed spatial characterization of neuroendocrine transformation with molecular validation in a nationwide cohort, we aim to identify distinct molecular subtypes of NEPC, discover biomarkers that may predict its development, and identify novel therapeutic targets.<\/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 Predicting and Treating NEPC<\/h3>\n\n\n\n

Our ultimate goal is not merely to diagnose NEPC after it develops, but to predict which prostate cancers are likely to undergo neuroendocrine transformation and intervene before this transition occurs.<\/p>\n\n\n\n

We aim to validate findings from patient-derived tumor specimens using experimental models, including patient-derived xenografts (PDXs) and organoids, and translate these insights into novel diagnostic and therapeutic strategies.<\/p>\n\n\n\n

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

Related papers<\/h2>\n\n\n\n

Enzaalutamide promotes an early plasticity-associated transcriptional state without terminal<\/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 canceler<\/strong>
Watanabe R, Shigehisa R, Kawada T, Yamamoto s, Kataya 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 a highly treatment-resistant fo […]<\/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-731","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\/731","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=731"}],"version-history":[{"count":2,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/731\/revisions"}],"predecessor-version":[{"id":734,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/731\/revisions\/734"}],"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=731"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}