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Current treatment and novel insights regarding ROS1-targeted therapy in malignant tumors
Shizhe Li1, He Zhang1, Ting Chen1
1Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Background:
The proto-oncogene ROS1 encodes an intrinsic type I membrane protein of the tyrosine kinase/insulin receptor family. ROS1 facilitates the progression of various malignancies via self-mutations or rearrangements. Studies on ROS1-directed tyrosine kinase inhibitors have been conducted, and some have been approved by the FDA for clinical use. However, the adverse effects and mechanisms of resistance associated with ROS1 inhibitors remain unknown. In addition, next-generation ROS1 inhibitors, which have the advantage of treating central nervous system metastases and alleviating endogenous drug resistance, are still in the clinical trial stage.
Method:
In this study, we searched relevant articles reporting the mechanism and clinical application of ROS1 in recent years; systematically reviewed the biological mechanisms, diagnostic methods, and research progress on ROS1 inhibitors; and provided perspectives for the future of ROS1-targeted therapy.
Results:
ROS1 is most expressed in malignant tumours. Only a few ROS1 kinase inhibitors are currently approved for use in NSCLC, the efficacy of other TKIs for NSCLC and other malignancies has not been ascertained. There is no effective standard treatment for adverse events or resistance to ROS1-targeted therapy. Next-generation TKIs appear capable of overcoming resistance and delaying central nervous system metastasis, but with a greater incidence of adverse effects.
Conclusions:
Further research on next-generation TKIs regarding the localization of ROS1 and its fusion partners, binding sites for targeted drugs, and coadministration with other drugs is required. The correlation between TKIs and chemotherapy or immunotherapy in clinical practice requires further study.
Insights
ROS1 inhibitors show promise in treating cancers like NSCLC, but challenges remain. Further research is needed to understand adverse effects, resistance mechanisms, and optimize next-generation therapies for better patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- ROS1 proto-oncogene encodes a tyrosine kinase involved in various malignancies.
- Approved ROS1 inhibitors exist for NSCLC, but resistance and side effects are concerns.
- Next-generation ROS1 inhibitors are in trials for CNS metastases and resistance, but require further study.
Purpose of the Study:
- To systematically review the biological mechanisms and clinical applications of ROS1 inhibitors.
- To analyze the research progress and future perspectives of ROS1-targeted therapy.
- To identify knowledge gaps regarding adverse effects and resistance mechanisms of ROS1 inhibitors.
Main Methods:
- Systematic literature search for recent articles on ROS1 and its inhibitors.
- Review of biological mechanisms, diagnostic methods, and clinical applications.
- Analysis of current research progress and future directions in ROS1-targeted therapy.
Main Results:
- ROS1 is highly expressed in malignant tumors, with limited approved inhibitors for NSCLC.
- Efficacy of existing ROS1 inhibitors in other cancers is not fully established.
- Next-generation inhibitors may overcome resistance and CNS metastasis but have increased adverse effects.
Conclusions:
- Further research on next-generation ROS1 inhibitors is crucial, focusing on drug-target interactions and combination therapies.
- Understanding ROS1 localization, fusion partners, and drug binding sites is essential.
- Clinical studies are needed to evaluate the correlation between ROS1 inhibitors, chemotherapy, and immunotherapy.
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