Therapeutic advances in the targeting of ROR1 in hematological cancers

  • Cell Death Discov. 2024 Nov 17;10(1):471. doi: 10.1038/s41420-024-02239-1.
Adrian-Bogdan Tigu  1 ,  Raluca Munteanu  1 ,  Cristian Moldovan  1 ,  Drula Rares  2 ,  David Kegyes  1 ,  Radu Tomai  1 ,  Vlad Moisoiu  3 ,  Gabriel Ghiaur  4 ,  Ciprian Tomuleasa  5 ,  Hermann Einsele  1  6 ,  Diana Gulei  1 ,  Carlo M Croce  7
Affiliations
  • 1. Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca, Cluj Napoca, Romania.
  • 2. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 3. Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
  • 4. Division of Hematological Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • 5. Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca, Cluj Napoca, Romania. [email protected].
  • 6. Department of Medicine, University of Würzburg, Würzburg, Germany.
  • 7. Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA. [email protected].
PMID: 39551787 DOI: 10.1038/s41420-024-02239-1
Abstract

Receptor Tyrosine Kinases (RTKs) are key cell surface receptors involved in cell communication and signal transduction, with great importance in cell growth, differentiation, survival, and metabolism. Dysregulation of RTKs, such as EGFR, VEGFR, HER2 or ROR, could lead to various diseases, particularly cancers. ROR1 has emerged as a promising target in hematological malignancies. The development of ROR1 targeted therapies is continuously growing leading to remarkable novel therapeutical approaches using mAbs, antibody-drug conjugates, several small molecules or CAR T cells which have shown encouraging preclinical results. In the hematological field, mAbs, small molecules, BiTEs or CAR T cell therapies displayed promising outcomes with the clinical trials data encouraging the use of anti-ROR1 therapies. This paper aims to offer a comprehensive analysis of the current landscape of ROR1-targeted therapies in hematological malignancies marking the innovative approaches with promising preclinical and clinical. Offering a better understanding of structural and functional aspects of ROR1 could lead to new perspectives in targeting a wide spectrum of malignancies.

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