Emerging tyrosine kinase inhibitors for the treatment of renal cancer

Abstract

Despite the development of more potent and more specific VEGFR TKIs, all tumors ultimately develop resistance to therapy and a plateau has been reached in terms of overall survival. Current research effort to develop new agents aims at overcoming both the primary and the acquired resistance to anti-VEGFR TKIs focusing on new molecular pathways. The ultimate goal is not only to improve patient outcome but to achieve durable complete remission. Several pitfalls that have been responsible for failure of other compounds remain, especially the lack of strong predictive biomarkers and the use of inappropriate tumor assessment criteria that may not accurately capture response to these new therapies.

Metabolic alterations in renal cell carcinoma

“…The downstream HGF/MET effectors involve the activation of RAS-MAPK and PI3K/Akt signaling pathways, the phosphorylation of STAT3 and JNK, and a cross-talk with EGFR and numerous membrane proteins (Plexin-B, CD44, a6b4 integrin) involved in a constant interaction with extracellular environment signals, promoting tumor cell proliferation, survival, invasion and angiogenesis [110,111].…”

YTHDC1 is downregulated by the YY1/HDAC2 complex and controls the sensitivity of ccRCC to sunitinib by targeting the ANXA1-MAPK pathway

“…Although surgical treatment is the mainstay of treatment for renal cancer, patients with unresectable advanced renal cancer or recurrent renal cancer rely on systemic treatment, typically antiangiogenic or immunotherapeutic treatment, to prolong their lives [ 2 , 3 ]. Tyrosine kinase inhibitors (TKIs) such as sunitinib are multitarget antiangiogenic agents in renal carcinoma cells [ 4 ]. TKIs are widely used in the treatment of advanced/metastatic renal cancer [ 4 ].…”

“…Tyrosine kinase inhibitors (TKIs) such as sunitinib are multitarget antiangiogenic agents in renal carcinoma cells [ 4 ]. TKIs are widely used in the treatment of advanced/metastatic renal cancer [ 4 ]. However, resistance to TKIs is common in the clinic, particularly after long-term treatment [ 5 ].…”