Multi‑kinase inhibitors and cisplatin for head and neck cancer treatment in vitro

Abstract

Multidrug resistance (MDR) remains one of the major causes of suboptimal outcome following therapy in head and neck squamous cell carcinoma (HNSCC). ATP-binding cassette (ABC) transporters are overexpressed in HNSCC, which contributes to the limited effect of chemotherapeutic treatment. In addition to their named function, tyrosine kinase inhibitors (TKIs) have been revealed to impact on ABC transporter activity and expression. Therefore, the present study aimed to investigate the effects of combination therapy using different TKIs combined with cisplatin. Reverse transcription-quantitative PCR was used to characterize ABC transporter and receptor expression in 5 HNSCC cell lines treated with 3 different TKIs (pazopanib, dovitinib, nintedanib) and cisplatin. Treatment efficacy was analyzed using a crystal violet staining assay. Analysis of ABC transporter (ABCB1, ABCC1 and ABCG2) genetic alterations was performed using The Cancer Genome Atlas. Statistical analysis was conducted to evaluate the effects of mono- and combination treatment. With the exception of ABCB1, all of the investigated ABC transporters were expressed in each cell line. The additive effects of TKI + cisplatin combination treatment were observed for pazopanib in three cell lines, nintedanib in four cell lines, and were not observed for dovitinib in any of the cell lines investigated. The combination of multi-kinase inhibitors and conventional chemotherapy in HNSCC may strengthen the use of current therapeutic strategies; nintedanib appears to be the most suitable TKI for combination therapy. Further efforts are required to classify TKI efficacy with regard to cisplatin resistance.

Urinary bladder cancer treatment by artemisinin and its combination with cisplatin exhibit a potent anti-cancer effect in male albino mice

“…In a previous study, [30] has demonstrated that dihydroartemisinin (derivative of artemisinin) caused an apoptosis in nonsmall cell lung cancer cells with EGFR or RAS mutation in-vitro and in-vivo. [31] found that after cisplatin treatment intermediate and low levels of FGFR3 and FGFR4 were expressed in all ve head and neck squamous cell carcinoma cell lines. Where, tumor growth or neoangiogenesis, as angiogenesis serves is a critical role in tumor growth, and the inhibition of this process via cisplatin alone is insu cient.…”

Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck

“…Preclinically, an in vitro study investigated the combination of various MKIs with cisplatin in SCCHN cell lines. Nintendanib was noted to exert the greatest synergistic effect with cisplatin chemotherapy ( 70 ). Phase I trials in patients with head and neck cancer showed adequate tolerance ( 71 , 72 ).…”

Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers

“…In preclinical models of OSCC, combination therapy of cisplatin and inhibitors of VEGFR (i.e., pazopanib and nintedanib) was more potent than treatment with chemotherapy alone ( 38 ). The efficacy and toxicity of docetaxel with or without vandetanib, an inhibitor of VEGFR, RET, and EGFR, was investigated in patients with advanced recurrent or metastatic HNSCC.…”