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Sacituzumab govitecan in triple-negative breast cancer: from bench to bedside, and back
Valentina Rossi1, Alessandra Turati1, Antonio Rosato1,2
1Immunology and Molecular Oncology Unit, Veneto Institute of Oncology (IOV)-IRCCS, Padova, Italy.
Abstract:
Triple-negative breast cancer (TNBC) represents a major therapeutic challenge due to its heterogeneous and aggressive phenotype, and limited target-specific treatment options. The trophoblast cell surface antigen (Trop-2), a transmembrane glycoprotein overexpressed in various cancers, has emerged as a promising target for TNBC. Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) that targets Trop-2, has recently entered treatment algorithms for advanced and metastatic TNBC, independently from Trop-2 expression status, with manageable toxicity. Despite the impressive results, questions remain unsolved regarding its efficacy, safety profile, and Trop-2 biological role in cancer. Currently, Trop-2 cannot be designated as a predictive biomarker in SG treatment, albeit its expression correlates with disease outcome, yet its levels are not uniform across all TNBCs. Additionally, data regarding Trop-2 expression variations in primary and metastatic sites, and its interplay with other biomarkers are still ambiguous but mandatory in light of future applications of SG in other indications and settings. This poses the questions of a careful evaluation of the efficacy and toxicity profile of SG in such early stages of disease, and in personalized and combinatorial strategies. Research and clinical data are mandatory to address SG drawbacks and minimize its benefits, to realize its full potential as therapeutic agent in different epithelial tumors.
Insights
Sacituzumab govitecan (SG) shows promise for triple-negative breast cancer (TNBC) by targeting Trop-2. Further research is needed to fully understand its efficacy, safety, and Trop-2
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and lack of targeted treatments.
- Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein overexpressed in many cancers, making it a potential therapeutic target.
- Sacituzumab govitecan (SG), a Trop-2 targeting antibody-drug conjugate (ADC), is now used for advanced and metastatic TNBC, demonstrating manageable toxicity.
Purpose of the Study:
- To critically evaluate the efficacy and safety profile of Sacituzumab govitecan (SG) in treating triple-negative breast cancer (TNBC).
- To investigate the biological role of Trop-2 in cancer and its utility as a predictive biomarker for SG treatment.
- To explore the potential of SG in earlier stages of disease and in personalized or combinatorial therapeutic strategies.
Main Methods:
- Review of current clinical data and research findings on Sacituzumab govitecan (SG) for TNBC treatment.
- Analysis of Trop-2 expression patterns in primary and metastatic TNBC sites.
- Assessment of the interplay between Trop-2 expression and other biomarkers.
Main Results:
- SG has demonstrated impressive results in advanced and metastatic TNBC, irrespective of Trop-2 expression levels.
- Trop-2 expression correlates with disease outcomes but is not uniform across all TNBC cases, limiting its role as a predictive biomarker.
- Unanswered questions remain regarding SG's long-term efficacy, safety, and the precise biological function of Trop-2.
Conclusions:
- While SG offers a valuable therapeutic option for TNBC, further research is essential to address its limitations and optimize its use.
- Understanding Trop-2 expression variability and its interaction with other biomarkers is crucial for future applications of SG.
- Comprehensive clinical data is needed to fully realize the potential of SG in various epithelial tumors and treatment settings.
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