Three minutes to ROR1

Basic Overview and Importance of ROR1

ROR1 (Receptor Tyrosine Kinase-Like Orphan Receptor 1) is a non-classical receptor tyrosine kinase belonging to the ROR family, which includes ROR1 and ROR2. These receptors play crucial roles in physiological and pathological processes such as cell signaling, embryonic development, neurogenesis, and tumorigenesis. Unlike conventional receptor tyrosine kinases, ROR1 lacks intrinsic kinase activity and is thus classified as an "orphan" receptor. Despite this, ROR1 regulates intracellular signaling by forming complexes with other molecules, influencing cellular proliferation, differentiation, migration, and survival.

The functional significance of ROR1 has been extensively studied in embryonic development, nervous system formation, and cancer. Recently, its potential as a tumor biomarker and therapeutic target has gained attention. Research shows aberrant ROR1 expression in various cancers, particularly aggressive malignancies, where its overexpression correlates with tumor invasiveness, metastasis, and poor prognosis. Consequently, ROR1 has emerged as a critical target in cancer research, with targeted therapies offering promising breakthroughs.

Molecular Structure and Function of ROR1

ROR1 features a complex molecular architecture comprising multiple domains:

• Extracellular region: Contains cysteine-rich domains, including Ig-like (immunoglobulin-like) and FSR (fibronectin type III) domains. The Ig-like domain facilitates ligand binding, while FSR domains mediate interactions with other signaling molecules.
• Transmembrane domain: Anchors ROR1 to the cell membrane. Although lacking kinase activity, this region is essential for signal transduction.
• Intracellular region: Includes a tyrosine kinase-like domain. Despite its catalytically inactive nature, this domain interacts with signaling molecules, adaptor proteins, and transcription factors to modulate downstream pathways such as Wnt/β-catenin, PI3K/Akt, and Ras/MAPK, thereby regulating cell proliferation, survival, and differentiation.

Role of ROR1 in Embryonic Development

ROR1 is vital during embryogenesis, particularly in nervous and skeletal system formation. Its expression peaks in early developmental stages but declines postnatally, persisting only in specific tissues (e.g., neural cells and certain tumors).

During embryogenesis, ROR1 modulates the Wnt/β-catenin pathway to influence cell proliferation, polarity, and fate determination—key processes in axial patterning and organogenesis. In neurodevelopment, ROR1 governs neuronal migration and differentiation; its deficiency in mice leads to severe neural defects, underscoring its indispensable role.

ROR1 and Cancer

Dysregulated ROR1 expression is a hallmark of many malignancies. It is highly expressed in hematologic cancers (e.g., chronic lymphocytic leukemia [CLL], acute lymphocytic leukemia [ALL]) and solid tumors (e.g., breast, lung, ovarian, and gastric cancers).

Overexpressed ROR1 drives tumor aggressiveness by promoting proliferation, migration, invasion, and therapy resistance. Mechanistically, it activates Wnt/β-catenin and PI3K/Akt pathways to enhance survival and anti-apoptotic signals, positioning ROR1 as both a diagnostic marker and therapeutic target.

ROR1 in Cancer Immunotherapy

The tumor-specific overexpression of ROR1 has spurred interest in immunotherapy. Current strategies include:

• Monoclonal antibodies: Anti-ROR1 antibodies (e.g., cirmtuzumab) exploit antibody-dependent cellular cytotoxicity (ADCC) to target cancer cells, with clinical trials underway for CLL.
• Cell-based therapies: ROR1-targeted CAR-T cells have shown efficacy in preclinical models.
• Small-molecule inhibitors: Agents disrupting ROR1-mediated signaling pathways are under investigation.

Clinical Prospects and Challenges

Despite its promise, ROR1-targeted therapies face hurdles:

• On-target/off-tumor effects: Low but detectable ROR1 expression in neural and immune cells raises safety concerns.
• Mechanistic gaps: Full elucidation of ROR1's signaling networks is needed to optimize therapeutic strategies.

Conclusion

As a non-canonical receptor tyrosine kinase, ROR1 is pivotal in development and cancer. Its tumor-specific overexpression and functional roles make it an attractive therapeutic target. Emerging modalities like antibodies and CAR-T cells hold potential, while ongoing research aims to overcome clinical challenges, paving the way for innovative cancer treatments.

Click on the product catalog numbers below to access detailed information on our official website.

Product Information