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Rationale for Prostate-Specific-Membrane-Antigen-Targeted Radionuclide Theranostic Applied to Metastatic Clear Cell
Anne Laure Giraudet1, Armelle Vinceneux1, Valentin Pretet1
1Centre Léon Bérard, 69008 Lyon, France.
Abstract:
Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC.
Insights
Prostate-specific membrane antigen (PSMA) targeted therapy shows promise for metastatic clear cell renal cell carcinoma (mccRCC). This approach, successful in prostate cancer, may offer new hope for mccRCC patients resistant to current treatments.
Area of Science:
- Oncology
- Nuclear Medicine
- Uro-oncology
Background:
- Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic aggressive prostate adenocarcinoma and tumor neovasculature, including in clear cell renal cell carcinoma (ccRCC).
- PSMA-targeted radioligand therapy (PRLT) with lutetium 177 has shown a survival benefit in metastatic prostate cancer.
- Current treatments for metastatic ccRCC (mccRCC), such as tyrosine kinase inhibitors and immunotherapy, have limitations for patients with progressive disease.
Purpose of the Study:
- To explore the rationale for applying PRLT to the treatment of metastatic clear cell renal cell carcinoma (mccRCC).
- To identify potential new therapeutic strategies for mccRCC patients who have progressed on existing therapies.
Main Methods:
- Review of existing literature on PSMA expression in ccRCC.
- Analysis of the efficacy and safety data from PSMA-targeted therapies in other solid tumors, particularly prostate cancer.
- Discussion of the biological basis for targeting PSMA in mccRCC neovasculature.
Main Results:
- PSMA is demonstrably overexpressed in the neovasculature of ccRCC, making it a potential therapeutic target.
- The success of PRLT in prostate cancer suggests a similar potential efficacy in other PSMA-expressing tumors.
- PRLT offers a novel mechanism of action distinct from current mccRCC treatments.
Conclusions:
- PRLT represents a promising therapeutic avenue for metastatic clear cell renal cell carcinoma (mccRCC).
- Further clinical investigation is warranted to evaluate the efficacy and safety of PRLT in mccRCC patients.
- Targeting PSMA could overcome resistance mechanisms observed with current anti-cancer therapies for mccRCC.
