Transmembrane receptor ROR1 as a therapeutic target in endometrial cancer

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Abstract

Endometrial cancer remains one of the most prevalent malignant neoplasms of the female reproductive system. Despite advancements in diagnostics and treatment, aggressive subtypes of the disease are characterized by high rates of metastasis, recurrence, and decreased overall survival, underscoring the need for novel therapeutic targets. One such promising molecular factor is the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is normally expressed predominantly in embryonic tissues but reactivates in various malignancies, including endometrial cancer.

ROR1 plays a role in the activation of key signaling pathways such as PI3K/Akt/mTOR, MAPK, and Wnt/β-catenin, regulating processes like cell proliferation, apoptosis, invasion, and epithelial-mesenchymal transition. High ROR1 expression correlates with unfavorable clinicopathological features, including high tumor grade, advanced FIGO stages, and decreased overall survival. Moreover, ROR1 contributes to chemoresistance by activating anti-apoptotic Bcl-2 family proteins and supporting inflammatory microenvironment signaling.

This article provides a comprehensive review of the molecular mechanisms involving ROR1, its role in oncogenesis and endometrial cancer progression, and its potential as both a prognostic biomarker and therapeutic target. Current approaches to targeted therapy are discussed, including the application of antibody–drug conjugates such as zilovertamab vedotin, and their prospects for clinical implementation. Given the significance of ROR1 in endometrial cancer pathogenesis, its inhibition may serve as the basis for personalized treatment strategies aimed at overcoming resistance and improving prognosis in patients with aggressive forms of endometrial cancer.

About the authors

Vladislav S. Skossyrskiy

I.M. Sechenov First Moscow State Medical University

Email: onco.vlad@gmail.com
ORCID iD: 0000-0002-3417-2359
SPIN-code: 6910-0652
Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Ilsina I. Gilmutdinova

I.M. Sechenov First Moscow State Medical University

Email: ilsinagilmutdinova815@gmail.com
ORCID iD: 0000-0002-7215-5066
Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Maxim S. Boot

I.M. Sechenov First Moscow State Medical University

Email: but_mc@mail.ru
ORCID iD: 0009-0000-8468-2106
SPIN-code: 1292-2693
Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Polina I. Zelenchenkova

I.M. Sechenov First Moscow State Medical University

Email: zelenchenkovapi@yandex.ru
ORCID iD: 0000-0002-9491-318X
SPIN-code: 8553-3232
Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Valeriia V. Kimutsadze

I.M. Sechenov First Moscow State Medical University

Email: lerunya-999@mail.ru
ORCID iD: 0009-0001-4084-3921
Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Veronika V. Kimutsadze

I.M. Sechenov First Moscow State Medical University

Email: veronika_kimutsadze@mail.ru
ORCID iD: 0009-0006-7791-4881
Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Evgeniia A. Svidinskaya

I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: svidinskaya@gmail.com
ORCID iD: 0000-0002-2368-1932
SPIN-code: 3002-6388

MD, Cand. Sci. (Medicine)

Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Mikhail B. Ageev

I.M. Sechenov First Moscow State Medical University

Email: mikhaageev@yandex.ru
ORCID iD: 0000-0002-6603-804X
SPIN-code: 3122-7420

MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

Elena A. Sosnova

I.M. Sechenov First Moscow State Medical University

Email: sosnova-elena@inbox.ru
ORCID iD: 0000-0002-1732-6870
SPIN-code: 6313-9959

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 8 Trubetskaya st, bldg 2, Moscow, 119991

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2. Fig. 1. Scheme of pathogenesis and signaling pathways activated by ROR1.

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