Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells

ABSTRACT

Introduction: There is a high expression of receptor tyrosine kinase like orphan receptor-1 (ROR-1), a tyrosine kinase receptor, in various tumor-cell types. ROR-1 is involved in many key processes in cancer including proliferation, survival and metastasis. Hence, ROR-1 is an attractive and promising therapeutic target. There are many therapeutic approaches that target ROR-1 and these include specific monoclonal antibodies (mAbs), modified T cells (CART cell), miRNAs and tyrosine kinase inhibitors (TKI).

Areas covered: This review examines ROR-1 structure and function, immunotherapeutic strategies including specific chimeric antigen receptor (CARs) T cells and miRNAs and other targeted approaches such as the use of tyrosine kinase inhibitors.

Expert opinion: Chimeric antibodies, CARs T cells, bi-specific T cell engagers (BiTEs), miRNAs and TKIs are used to target the ROR-1 marker on cancer cell lines. By selecting the most favorable therapeutic approaches regarding ROR-1 in vivo, anti-ROR-1 antibodies or CAR T cells can be also used for diagnosis of ROR-1⁺ cancer cells in new technologies such as biosensors. Moreover, ROR-1 targeted combination therapy with other cancer biomarkers could be considered a novel therapeutic strategy for cancer treatment.

KEYWORDS:

• Receptor tyrosine kinas like orphan
• ROR-1
• targeted therapy
• immunotherapy
• cancer

Article Highlights

• ROR-1 is a useful biomarker for cancer diagnosis and targeted therapy

• The large extracellular region of ROR-1 provides large numbers of epitopes for different immune responses such as antibody-dependent cell mediated cytotoxicity, complement-dependent cytotoxicity, and apoptosis for immunotherapy.

• Specific Chimeric Antigen Receptor (CARs) T cells offer a novel therapeutic approach.

• miRNAs can regulate ROR-1 expression in many cancers.

• ROR-1 tyrosine kinase inhibitors (TKIs) increase apoptosis in progressive and non- progressive cancer cells while normal cells are unaffected.

• TKIs open new promising avenues for cancer therapy.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to acknowledge Stem Cell Research Center and Department of Immunology at Tabriz University of Medical Sciences (Iran) for their great help.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was supported by the Stem Cell Research Center at Tabriz University of Medical Sciences, Tabriz, Iran [Grant No. 60987].