Anti-KIT polyclonal antibody [Biotin]

Background There are limited treatment options for unresectable recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Vascular endothelial growth factor is of significant interest for targeted therapy in R/M HNSCC because of its central role in tumorigenesis and immunosuppression. Axitinib is a potent inhibitor of vascular endothelial growth factor receptor (VEGFR) 1 , VEGFR2, VEGFR3, platelet-derived growth factor receptor, as well as c-kit and offers such an approach. Methods This article reports the results of a phase 2 trial evaluating axitinib in R/M HNSCC according to the Choi criteria for radiographic response assessment. The primary endpoint of this trial was 6-month overall survival. RESULTS Twenty-nine patients were enrolled, and 28 were evaluable for a response. Patients were heavily pretreated with 61% having had at least 1 previous systemic treatment in the metastatic setting (range, 0-5). The median overall survival of 9.8 months and the 6-month overall survival rate of 70% met the protocol-defined criteria for clinical efficacy. The best overall response rate was 42%. Correlative analyses demonstrated that PI3K signaling pathway alterations were associated with an increased response to therapy (75% vs 17%). A marked response to therapy was seen in a subgroup of patients who were treated with an immune checkpoint inhibitor after progression on axitinib. Conclusions Treatment with axitinib is associated with improved survival in patients with heavily pretreated head and neck cancer, and PI3K pathway alterations may serve as a biomarker for response. Further investigation is warranted to evaluate axitinib in biomarker-selected populations, especially in combination with immune checkpoint inhibitor therapy. Lay Summary Metastatic head and neck squamous cancer is an incurable disease with limited treatment options and a poor prognosis. This study is the first to demonstrate that the targeted oral drug axitinib improves survival in patients with heavily pretreated metastatic head and neck cancer. Furthermore, patients whose tumors have specific mutations derive the greatest benefit from therapy. The investigation of axitinib alone or in combination with immunotherapy in a genomic biomarker-selected population is warranted.

Non-small cell lung cancer (NSCLC) is a leading subtype of lung cancer, with high mortality rates. Recently, long non-coding RNAs (lncRNAs) have been associated with NSCLC. The present study aimed to examine the role of the TP73 antisense RNA 1 (TP73-AS1) lncRNA in NSCLC. TP73-AS1 and microRNA(miR)-34a-5p expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR) and chromogenicin situhybridization (CISH). Cell proliferation, apoptosis, migration and invasion was determined using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Matrigel assays, respectively. The median inhibitory concentration (IC50) value of cisplatin (cis-diamminedichloroplatinum; DDP) was assessed using a CCK-8 assay. The interaction between miR-34a-5p and TP73-AS1 or tripartite motif-containing 29 (TRIM29) was predicted usingmicroRNA.organd Starbase, then verified using a dual-luciferase reporter assay. The expression of TRIM29 was quantified at the mRNA and protein level using RT-qPCR and western blot analysis, respectively. TP73-AS1 was significantly upregulated, while miR-34a-5p was downregulated in NSCLC tissues and cells. Functionally, TP73-AS1 knockdown inhibited proliferation, migration, invasion and DDP resistance, whilst inducing apoptosis in NSCLC cells. miR-34a-5p was identified as a target for TP73-AS1, and its inhibition reversed the effects of TP73-AS1 knockdown on NSCLC cells. In addition, TRIM29 was targeted by miR-34a-5p, and its overexpression reversed the effects of miR-34a-5p. Moreover, TP73-AS1 acted as a molecular sponge for miR-34a-5p, increasing the expression of TRIM29. In conclusion, TP73-AS1 contributed to proliferation, migration and DDP resistance but inhibited apoptosis of NSCLC cells by upregulating TRIM29 and sponging miR-34a-5p.