Targeted Therapies in Advanced Renal Cell Carcinoma
Summary
Advanced renal cell carcinoma (RCC), particularly its clear-cell subtype, has historically carried a poor prognosis owing to intrinsic resistance to conventional chemotherapy. The advent of molecularly targeted agents has transformed management by exploiting key oncogenic pathways. Inhibitors of the vascular endothelial growth factor (VEGF) signalling axis, such as sunitinib, pazopanib and sorafenib, impede tumour angiogenesis and improve progression-free and overall survival. Parallel advances in inhibitors of the mammalian target of rapamycin (mTOR) pathway, including everolimus and temsirolimus, have offered alternatives for patients refractory to VEGF-directed therapy. More recently, multi-target tyrosine kinase inhibitors (TKIs) with activity against MET and AXL have addressed mechanisms of acquired resistance, while combinations of TKIs with immune checkpoint inhibitors have yielded further gains in efficacy. Despite these successes, optimal sequencing, biomarker-driven patient selection and management of treatment-related toxicities remain areas of active investigation. The global impact of targeted therapy is underscored by its incorporation into guidelines worldwide and by ongoing efforts to extend benefit through precision medicine and novel combinations.
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Targeted Therapies in Advanced Renal Cell Carcinoma publication trend
The graph below shows the total number of articles in targeted therapies in advanced renal cell carcinoma across all publications each year (not limited to Nature Index journals).
Technical terms
Tyrosine kinase inhibitor (TKI): A small-molecule drug that blocks signalling enzymes involved in tumour growth and angiogenesis.
Vascular endothelial growth factor (VEGF): A signalling protein that stimulates formation of new blood vessels, often overexpressed in tumours.
Progression-free survival (PFS): The length of time during which a patient’s disease does not worsen on treatment.
Immune checkpoint inhibitor: An antibody that blocks immune regulatory proteins, enhancing antitumour T-cell activity.
References
- Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduction and Targeted Therapy (2023).
- Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. Journal of Hematology & Oncology (2018).
- Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib. JAMA Oncology (2019).
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