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The receptor tyrosine kinase ROR1--an oncofetal antigen for targeted cancer therapy
Mohammad Hojjat-Farsangi1, Ali Moshfegh1, Amir Hossein Daneshmanesh1
1Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
Abstract:
Targeted cancer therapies have emerged as new treatment options for various cancer types. Among targets, receptor tyrosine kinases (RTKs) are among the most promising. ROR1 is a transmembrane RTK of importance during the normal embryogenesis for the central nervous system, heart, lung and skeletal systems, but is not expressed in normal adult tissues. However, ROR1 is overexpressed in several human malignancies and may act as a survival factor for tumor cells. Its unique expression by malignant cells may provide a target for novel therapeutics including monoclonal antibodies (mAbs) and small molecule inhibitors of tyrosine kinases (TKI) for the treatment of cancer. Promising preclinical results have been reported in e.g. chronic lymphocytic leukemia, pancreatic carcinoma, lung and breast cancer. ROR1 might also be an interesting oncofetal antigen for active immunotherapy. In this review, we provide an overview of the ROR1 structure and functions in cancer and highlight emerging therapeutic options of interest for targeting ROR1 in tumor therapy.
Insights
Receptor tyrosine kinase 1 (ROR1) is overexpressed in cancers but not normal adult tissues, making it a promising target for new cancer therapies like monoclonal antibodies and tyrosine kinase inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Receptor tyrosine kinases (RTKs) are key targets in cancer therapy.
- ROR1, a transmembrane RTK, is crucial in embryonic development but absent in adult tissues.
- ROR1 overexpression in malignancies suggests its role as a tumor cell survival factor.
Purpose of the Study:
- To review the structure and function of ROR1 in cancer.
- To highlight emerging therapeutic strategies targeting ROR1 for cancer treatment.
Main Methods:
- Literature review of ROR1 structure, function, and expression in cancer.
- Analysis of preclinical data for ROR1-targeted therapies.
- Overview of ROR1 as an oncofetal antigen for immunotherapy.
Main Results:
- ROR1's unique expression pattern in malignant cells offers a specific therapeutic target.
- Preclinical studies show promise for ROR1-targeting agents in chronic lymphocytic leukemia, pancreatic, lung, and breast cancers.
- ROR1's potential as an oncofetal antigen for active cancer immunotherapy is highlighted.
Conclusions:
- ROR1 is a validated target for novel cancer therapeutics.
- Targeting ROR1 with monoclonal antibodies or small molecule inhibitors holds significant therapeutic potential.
- ROR1-based immunotherapy presents a promising avenue for cancer treatment.
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