Therapeutic potential of targeting the oncofetal antigen ROR1

Abstract

The increasing prevalence of drug resistant cancers to conventional therapies remains a major challenge in oncology, emphasizing the need for further research and treatment development. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) presents as a particularly suitable target for cancer therapy, as this type I transmembrane protein is expressed during embryogenesis and up-regulated in various solid and hematological malignancies, but generally repressed in normal adult tissues. A growing cancer literature has established ROR1 as a contributor to cell metastasis and a survival factor for malignant cells, suggesting the therapeutic potential in targeting ROR1 for cancer therapy. The tumor-selective expression of ROR1 has encouraged investigation of novel ROR1-targeted therapies including monoclonal antibodies, small molecule inhibitors, and chimeric antigen receptor T-cells, and preclinical trials have supported their safety and efficacy in inducing tumor growth suppression. Despite these advances in therapeutics, the role of ROR1 in oncogenic signaling is not yet fully understood. Through a comprehensive examination of ROR1 literature, this review will examine the biology of ROR1 as it relates to tumor progression, and demonstrate the viability of current ROR1-targeted therapies.