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Submitted On:

August 4, 2025

Published On:

August 8, 2025

Updated On:

August 8, 2025

Correspondence:

Xun Liao, Tianfu Jincheng Laboratory, Chengdu, 610093, China

Citation

Hong W, Jia Y, Xiaoxia H, et al. ROR1 as an emerging therapeutic target in oncology: biology and clinical drug development. Int J Gen Clin Med. 2025;1(1):1–6.

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ROR1 as an emerging therapeutic target in oncology: biology and clinical drug development

Abstract
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen with minimal adult tissue expression but critical roles in cancer progression through Wnt5a, PI3K/AKT, and Hippo-YAP/TAZ pathways. Its selective tumor expression makes ROR1 an attractive therapeutic target across hematologic and solid malignancies. Multiple modalities have advanced clinically, with antibody-drug conjugates (ADC) leading development. Zilovertamabvedotin achieved unprecedented complete response rates in lymphomas, while CAR-T therapies demonstrate efficacy in hematologic cancers with limited solid tumor penetration. Bispecific T-cell engagersand novel platforms including logic-gated CAR-Ts and dual-control ADCs address current limitations. Despite challenges such as on-target/off-tumor effects and heterogeneous expression patterns, ROR1-targeted therapies represent a rapidly evolving precision oncology frontier with transformative potential across ROR1-positive malignancies.

Keywords: ROR1, Zilovertamab, ADC, CAR-T, Targeted therapy

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