Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas
Kidney cancers comprise about 3% of all new malignancies in the United States. Renal cell carcinomas (RCCs) are the most common type of renal malignancy making up about 85% of kidney cancer cases. Signs and symptoms of renal cell carcinomas can result from local tumor growth, paraneoplastic syndrome...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824001257 |
| _version_ | 1827267180084854784 |
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| author | Robert Roskoski, Jr. |
| author_facet | Robert Roskoski, Jr. |
| author_sort | Robert Roskoski, Jr. |
| collection | DOAJ |
| description | Kidney cancers comprise about 3% of all new malignancies in the United States. Renal cell carcinomas (RCCs) are the most common type of renal malignancy making up about 85% of kidney cancer cases. Signs and symptoms of renal cell carcinomas can result from local tumor growth, paraneoplastic syndromes, or distant metastases. The classic triad of presentation with flank pain, hematuria, and a palpable abdominal mass occurs in fewer than 10% of patients. Most diagnoses result from incidental imaging findings (ultrasonography or abdominal CT imaging) performed for another reason. Localized disease is treated by partial nephrectomy, total nephrectomy, or ablation (tumor destruction with heat or cold). When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting programed cell death protein 1, PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting PD1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors. |
| first_indexed | 2024-04-24T08:14:25Z |
| format | Article |
| id | doaj.art-df61a1d164a24d3c9532c1938e622b44 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2025-03-22T04:29:38Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-df61a1d164a24d3c9532c1938e622b442024-04-28T04:41:45ZengElsevierPharmacological Research1096-11862024-05-01203107181Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomasRobert Roskoski, Jr.0Blue Ridge Institute for Medical Research, 221 Haywood Knolls Drive, Hendersonville, NC 28791, United StatesKidney cancers comprise about 3% of all new malignancies in the United States. Renal cell carcinomas (RCCs) are the most common type of renal malignancy making up about 85% of kidney cancer cases. Signs and symptoms of renal cell carcinomas can result from local tumor growth, paraneoplastic syndromes, or distant metastases. The classic triad of presentation with flank pain, hematuria, and a palpable abdominal mass occurs in fewer than 10% of patients. Most diagnoses result from incidental imaging findings (ultrasonography or abdominal CT imaging) performed for another reason. Localized disease is treated by partial nephrectomy, total nephrectomy, or ablation (tumor destruction with heat or cold). When the tumors have metastasized, systemic therapy with protein-tyrosine kinase antagonists including sorafenib, sunitinib, pazopanib, and tivozanib that target vascular endothelial, platelet-derived, fibroblast, hepatocyte, and stem cell factor growth factor receptors (VEGFR, PDGFR, FGFR, MET, and Kit) were prescribed after 2005. The monoclonal antibody immune checkpoint inhibitor nivolumab (targeting programed cell death protein 1, PD1) was approved for the treatment of RCCs in 2015. It is usually used now in combination with ipilimumab (targeting CTLA-4) or cabozantinib (a multikinase blocker). Other combination therapies include pembrolizumab (targeting PD1) and axitinib (a VEGFR and PDGFR blocker) or lenvatinib (a multikinase inhibitor). Since the KEYNOTE-426 clinical trial, the use of immune checkpoint inhibitors in combination with protein-tyrosine kinase inhibitors is now the standard of care for most patients with metastatic renal cell carcinomas and monotherapies are used only in those individuals who cannot receive or tolerate immune checkpoint inhibitors.http://www.sciencedirect.com/science/article/pii/S1043661824001257AvelumabBevacizumabIpilimumabNivolumabPembrolizumabVasculogenesis |
| spellingShingle | Robert Roskoski, Jr. Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas Pharmacological Research Avelumab Bevacizumab Ipilimumab Nivolumab Pembrolizumab Vasculogenesis |
| title | Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas |
| title_full | Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas |
| title_fullStr | Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas |
| title_full_unstemmed | Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas |
| title_short | Combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas |
| title_sort | combination immune checkpoint and targeted protein kinase inhibitors for the treatment of renal cell carcinomas |
| topic | Avelumab Bevacizumab Ipilimumab Nivolumab Pembrolizumab Vasculogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824001257 |
| work_keys_str_mv | AT robertroskoskijr combinationimmunecheckpointandtargetedproteinkinaseinhibitorsforthetreatmentofrenalcellcarcinomas |