Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers

Selective expansion of renal cancer stem cells using microfluidic single-cell culture arrays for anticancer drug testing

“…The activation of the endoplasmic reticulum stress response and the induction of EMT are recognized as significant contributors to the development of resistance against VEGFR-targeted therapies. 34,35 Consequently, this resistance mechanism may enhance the tolerance of renal cancer stem cells towards tyrosine kinase inhibitors (TKIs). Hence, it becomes evident that TKIs primarily function to inhibit differentiated renal cancer cells, while their efficacy in eradicating renal cancer stem cells remains limited.…”

Sorafenib exhibits lower toxicity and comparable efficacy to sunitinib as a first-line treatment for metastatic renal cell carcinoma: A systematic review and meta-analysis

“…Although both sunitinib and sorafenib are multi-targeted TKIs, they exert their anti-tumor effects by disrupting the activity of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and stem cell growth factor receptor to impede tumor angiogenesis and inhibit tumor cell proliferation. [31,32] However, there are differences in their pharmacokinetic properties, such as bioavailability, elimination half-life, plasma concentration, time to peak concentration, plasma protein binding rate, and metabolic clearance pathways. [33] Therefore, the efficacy and safety of sorafenib and sunitinib in the treatment of mRCC remain controversial in clinical practice, especially in the first-line treatment.…”

Antineoplastic indole-containing compounds with potential VEGFR inhibitory properties

“…2) is an oral antitumor multi-targeted tyrosine kinase inhibitor (VEGFR-1,-2, -3; PDGFR-a, -b: plateletderived growth-factor receptor; and c-kit: stem cell factor receptor) against FLT3, which is an FMS-like tyrosine kinase inhibitor with potent anti-angiogenesis properties. 16,[37][38][39] It is clinically approved against advanced renal and imatinibresistant gastrointestinal (FDA approval in 2006) and pancreatic cancers (FDA approval in 2011). It has also been given FDA approval (2017) for adult adjuvant treatment at high risk of Fig.…”