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Repurposing denosumab in lung cancer beyond counteracting the skeletal related events: an intriguing perspective
Maria V Deligiorgi1, Dimitrios T Trafalis1
1Department of Pharmacology - Clinical Pharmacology Unit, National and Kapodistrian University of Athens, Faculty of Medicine , Athens, Greece.
Introduction:
Repurposing denosumab in lung cancer therapeutics capitalizes on its well-established role in preventing the skeletal related events (SREs) and its emerging, yet elusive, bone-independent role, assigned to inhibit the contribution of RANKL to cancer initiation and progression.
Areas Covered:
The present review presents the available preclinical and clinical data indicating that denosumab may provide survival benefit to lung cancer patients beyond the counteraction of SREs.
Expert Opinion:
Despite the preliminary data heralding the potential of denosumab to increase overall survival in lung cancer, the embracement of this strategy in clinical practice cannot be advocated until large randomized clinical trials consolidate its safety and efficacy. Given the improvement of lung cancer prognosis ascribed to revolutionary targeted treatment agents, the possibility of denosumab-related increased risk of second primary malignancies merits further evaluation. Many challenges in endorsing denosumab as a strategy to treat lung cancer beyond SREs prevention are pending counteraction, including: (i) patient selection guided by validated predictive and prognostic biomarkers; (ii) assessment of long-term outcomes; (iii) evaluation of benefit-risk ratio; (iv) translational research; (v) combination of denosumab with other targeted therapies; (vi) integration of genomic biomarkers, immune-related biomarkers, and biomarkers of active RANKL pathway to guide the decision-making process.
Insights
Denosumab shows potential for lung cancer survival benefits beyond preventing skeletal events. Further trials are needed to confirm safety and efficacy before widespread clinical use.
Area of Science:
- Oncology
- Pharmacology
Background:
- Denosumab is approved for preventing skeletal-related events (SREs) in cancer patients.
- Emerging evidence suggests a bone-independent role for denosumab in cancer therapy.
Purpose of the Study:
- To review preclinical and clinical data on denosumab's potential survival benefit in lung cancer.
- To explore denosumab's role beyond SRE prevention.
Main Methods:
- Review of existing preclinical and clinical studies on denosumab in lung cancer.
- Analysis of data regarding denosumab's efficacy and safety.
Main Results:
- Preliminary data suggest denosumab may improve overall survival in lung cancer patients.
- Denosumab's bone-independent mechanisms are still under investigation.
Conclusions:
- Denosumab shows promise for lung cancer treatment beyond SRE prevention.
- Large randomized trials are required to establish safety, efficacy, and optimal patient selection. Biomarker research is crucial for guiding treatment decisions.
