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Unlocking the potential: advancements and future horizons in ROR1-targeted cancer therapies

Lin Li1, Weixue Huang2, Xiaomei Ren2

  • 1State Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.

Science China. Life Sciences
|August 15, 2024
PubMed

Insights

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed in many cancers but not normal tissues, making it a promising target for new cancer therapies. Research is advancing ROR1-targeted drugs, including antibodies and small molecules, for improved tumor treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Receptor tyrosine kinase-like orphan receptor 1 (ROR1) shows elevated expression in various malignancies like leukemia, breast, ovarian, lung cancers, and melanoma.
  • Conversely, ROR1 is typically absent or minimally expressed in normal adult tissues.
  • This differential expression pattern highlights ROR1 as a prime target for selective anti-cancer therapies.

Purpose of the Study:

  • To provide an updated review of ROR1's structural and functional aspects.
  • To explore ROR1's role in embryonic development and cell survival pathways.
  • To discuss evolutionary strategies for targeting ROR1 in malignant tumors.

Main Methods:

  • Literature review of ROR1's biological roles and therapeutic targeting strategies.
  • Analysis of current clinical development of ROR1-directed therapeutics.
  • Exploration of small molecule inhibitors for PROTAC degrader development.

Main Results:

  • ROR1 is a validated target in multiple cancer types.
  • Several therapeutic modalities targeting ROR1 are in clinical development, including monoclonal antibodies, ADCs, and CAR-T therapies.
  • Small molecule inhibitors offer potential for developing novel PROTAC degraders.

Conclusions:

  • ROR1 represents a significant therapeutic target for a range of cancers.
  • Ongoing drug development efforts show promise for ROR1-based cancer treatments.
  • Further understanding of ROR1 biology may unlock advanced therapeutic strategies.
Keywords:
ROR1antibody drugsclinical trialspreclinical trialssignaling transductionsmall molecule inhibitors

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