Abstract
Purpose
In recent years, immune checkpoint blockade (ICB) therapies have shown good clinical responses in various solid cancers. However, a major challenge in the process of ICB treatment is when tumors do not have enough infiltrating T cells. Antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) and its receptors have been approved for the treatment of various malignant solid tumors alone or in combination with other therapies. Our review mainly discusses the preclinical rationale and clinical efficacy of antiangiogenic and ICB combination therapy in urogenital tumors.
Methods
We reviewed relevant literature on preclinical research and clinical trial results regarding antiangiogenic and ICB combination therapy in urogenital tumors from PubMed. In addition, we searched ongoing clinical trials on ClinicalTrials.gov to collect information related to this specific topic.
Results
Antiangiogenesis therapy could enhance T cell recruitment and increase T cell infiltration into the tumor microenvironment by blocking VEGF–VEGF receptor 2 binding and downstream signaling pathways to normalize tumor blood vessels. The combination of ICB and antiangiogenesis therapy could improve antitumor activity according to subsequent preclinical experiments and several phase I/II/III clinical trials on urogenital tumors.
Conclusion
Combined therapy has shown some antitumor efficacy in several urogenital tumors, such as metastatic renal cell carcinoma, metastatic urothelial and genitourinary tumors, endometrial carcinoma, ovarian cancer, and fallopian tube cancer. Combination therapy is a promising strategy that can be used to improve the therapeutic efficacy, and the identification of precise biomarkers of this combined therapy is the direction of future studies.
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YY, NZ and SSW contributed to the study conception and design. Literature searching and data analysis were performed by NZ, JW, JC, LY and XF. The first draft of the manuscript was written by NZ and the paper was revised by YY and SSW critically. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Zhu, N., Weng, S., Wang, J. et al. Preclinical rationale and clinical efficacy of antiangiogenic therapy and immune checkpoint blockade combination therapy in urogenital tumors. J Cancer Res Clin Oncol 145, 3021–3036 (2019). https://doi.org/10.1007/s00432-019-03044-5
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DOI: https://doi.org/10.1007/s00432-019-03044-5