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Abstract
Angiogenesis is a crucial process in the development of kidney cancer. Agents targeting angiogenesis have played an important role in the treatment of kidney cancer. Four lines of drugs have been proved in recent years. Although tumor resistance and side effect still exist, the survival rate have vastly increased. It is a good strategy for treatment of renal cancer.
Introduction
The aim of the paper is to explore the mechanism of angiogenesis and anti-angiogenesis therapy in the treatment of kidney cancer, discuss the merit and demerit of anti-angiogenesis therapy, and state the future direction of the therapy.
Angiogenesis is a crucial process in the development of kidney cancer. Agents targeting angiogenesis have played an important role in the treatment of kidney cancer. 1 Between pro- and anti- angiogenic mediators, there is an balance under normal physiologic conditions, which shifted towards either of them to promote physiological processes or as part of a pathological condition. Vascular endothelial growth factor (VEGF) and its signaling is considered the vital rate-limiting step of this process. The aim of newly formed blood vessels have two main functions: supply the tumor tissue with nutrients and provide pathway for cancer cells to metastasize. Renal cell carcinoma has been reported to be dependent on angiogenesis and respond well to anti-angiogenic therapies. Blocking the tyrosine kinase receptor or neutralizing angiogenic factors such as VEGF or its receptors are two main mechanisms of anti-angiogenesis therapy.2
Kidney cancer, renal caner, is a tumor that kidney cells become malignant and grow out of control. The most common type of kidney cancer is renal cell carcinoma which first appears in the lining of tubeles.3 80% of RCC is clear cell renal cell carcinoma (ccRCC) and 20% is non-clear cell carcinoma (nccRCC).4 Both two types are related with mutation of the VHL tumor suppressor gene on short arm of chromosome 3.5
Hypoxia-inducible factor-1? (HIF-1?), a transcription factor activated in response to tissue hypoxia, whose degradation can be promoted by VHL protein to prevent uncontrolled angiogenesis in normal cells.
The generation of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) is most notable among all the proangiogenic growth factors when triggered by accumulation of HIF-1 in renal tumors with mutated VHL gene.VEGF and PDGF then bind to its receptors and activate the endothelial cell proliferation, migration, and capillary tube formation,which would lead to uncontrolled cell growth and invasion of tumor as a consequence.6
Search strategy
Information of this paper were found from journals and books on NCBI, Pubmed, ScienceDriect, google scholar, frontiors, Journal of Hematology & Oncology. Library also has been visited to find relative information.
Discussion
Angiogenesis is an crucial part of renal tumor formation. As a consequence, anti-angiogenesis has been studied for decades. Although the survival rate was only 5-15% at the begining, the outcome improved significantly as further modification made to the therapy include reduced side effect and increased progression-free survival rates.1
Overall, the anti-VEGF threpies are well tolerated, but there are still many side effects including diarrhea, fatigue, nausea, stomatitis, hypertension, hand-foot skin reaction. These side effects could interrupt the therapy.6
Continued clinical investigation have shown major defect of anti-angiogenesis therapy in kidney cancer including inherent/acquired resistance due to compensation from parallel signaling pathways and induction of tumor invasiveness. Lack of biomarkers that can monitor the progression of tumor hurdles the track of therapy effectiveness.7
In my opinion, anti-angiogenesis therapy in kidney cancer is an developing treatment that have already receive successful. The outcome of improving survival rate was impressive. Lots of laboratory trials and researches on new generation of drugs are still going on. The survival rate will be increased and side effects will be decreased in the future.
Renal tumor was first caused by mutation of VHL gene. The gene silencing technology could be used to treat renal tumor.
Future Directions
Biomarkers that can be tracked throughout the treatment should be added to monitor the whole process and evaluate the effectiveness.
New drug which have lower drug resistance and less side effect should be researched and proved.Study renal tumor in subtype would allow greater precision for clinical trail design.1
Moreover, due to more new agents been approved, there are more management work the clinician must do to get optimal effects. They have to create different treatment plans which means combining different agents for different patients. 8