Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2, RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti-cancer effects in preclinical and clinical models of cancers derived from both epithelial and mesenchymal origins [prostate cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell carcinoma, etc.]. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurrence of drug resistance, combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results.
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PMID:Cabozantinib in Thyroid Cancer. 2615 49

The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups.
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PMID:Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience. 2790 50