Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients

Abstract

The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs.

Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial

“…Results from our previous study indicated that sunitinib-induced HFSR is likely to develop within 6 weeks of sunitinib initiation [22]. In this study, HFSR evaluated at weeks 3 and 6 was considered induced by sunitinib.…”

Association of Single Nucleotide Polymorphisms in <i>STAT3</i>, <i>ABCB1</i>, and <i>ABCG2</i> with Stomatitis in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib: A Retrospective Analysis in Japanese Patients

“…In recent works, sunitinib was reported to induce RCC cell apoptosis and to decrease immunosuppressive cell numbers as a result of STAT3 inhibition. 1,[24][25][26][27] STAT3 is activated by the stimulation of IL-6 and growth factors, and is then involved in the regulation of cellular differentiation, survival, and proliferation. 28,29) Immune systems such as Toll-like receptor signaling and B-cell receptor signaling and inflammatory cytokines relate to stomatitis development.…”

“…1) However, stomatitis is a very frequent complication associated with molecular-targeted drugs. Sunitinib, one of multiple tyrosine-kinase inhibitors currently used as first-line treatment for mRCC, is associated with stomatitis and has a reported incidence of 52% at any grades.…”

“…8) Signal transducer and activator of transcription (STAT) 3 is a point of convergence for the signaling pathways downstream of numerous cytokine receptors or tyrosine kinases, including vascular endothelial growth factor (VEGF) receptor, plateletderived growth factor receptor (PDGFR), epidermal growth factor receptor, and Src. 1,9,10) STAT3 regulates the expression of several genes involved in a variety of cellular responses including proliferation, differentiation, apoptosis, and wound healing. 11,12) Furthermore, it was reported that activating STAT3 can promote oral mucosal wound healing, 13) STAT3 may play a key role for regulating homeostasis of oral mucosa.…”

Effects of VEGF and VEGFR polymorphisms on the outcome of patients with metastatic renal cell carcinoma treated with sunitinib: a systematic review and meta-analysis

“…Besides, the initial clinical course of RCC is asymptomatic, resulting in 25–30% of patients presenting with metastatic disease when diagnosed [ 2 ]. Several molecular-targeted drugs have emerged as the first-line treatment for mRCC patients attributed to its insensitivity to chemotherapy and radiotherapy [ 3 – 6 ]. Sunitinib, as a small-molecule receptor tyrosine kinase inhibitor (TKI), gaining the approval of the Food and Drug Administration (FDA) in 2006.…”