Predicting Tumor Sensitivity to Chemotherapeutic Drugs in Oral Squamous Cell Carcinoma Patients

Abstract

Oral Squamous Cell Carcinoma (OSCC) patients respond poorly to chemotherapy. We analyzed the expression of 11 drug response-related genes in 31 OSCC biopsies, collected prior to any treatment, using custom-designed PCR array. Further, we investigated the drug response pattern of selected anticancer drugs by BH3 (Bcl2 Homology-3) profiling in the primary cells isolated from OSCC tissues. Then, we correlated the results of drug-response gene expression pattern with apoptotic priming to predict tumor response to chemotherapy. The best performing drug (BPD) and response differences (RD) between the drugs were identified using statistical methods to select the best choice of drug in a personalized manner. Based on the correlation, we classified OSCC tumors as sensitive (13 tumors), moderately responsive (16 tumors) or resistant (2 tumors) to chemotherapy. We found that up-regulation of genes linked with drug resistance facilitates survival of tumor samples, which was revealed by the percentage of apoptotic priming. Moreover, we found that paclitaxel-induced 40–45% apoptotic priming compared to other drugs. Average response difference (RD) analysis showed that 80% of tumors responded well to paclitaxel as compared to other drugs studied. Therefore, gene expression analysis with BH3 profiling reveals drug sensitivity that could be translated for drug selection before treatment.

Effect of TTLL12 on tubulin tyrosine nitration as a novel target for screening anticancer drugs<em> in&nbsp;vitro</em>

“…This novel assay can screen out new effective anticancer drugs and determine the anticancer molecular mechanism of these drugs. Paclitaxel exerts a notable therapeutic effect on OSCC and increases tubulin tyrosine nitration ( 28 , 29 ); thus, it was used as a positive control in the present study. Conversely, thiirene is not associated with tumors and does not affect tubulin tyrosine nitration ( 30 ); thus, it was used as a negative control in the present study.…”

“…Paclitaxel is known to exert a therapeutic effect on OSCC and increases tubulin tyrosine nitration ( 28 , 29 ); thus, it was used as a positive control in the present study. Thiirene was used as a negative control as it does not affect tubulin tyrosine nitration ( 30 ), and no evidence associating thiirene and tumor progression has been documented in the following: PubMed ( ), Web of Science ( ), Ovid ( ), Science Direct ( ), Wan Fang ( ) or the China National Knowledge Infrastructure databases ( ).…”

Emerging functions and clinical applications of exosomes in human oral diseases

“…Paclitaxel, performing best to induce the apoptosis of OSCC cells (40-50%) in comparison with daunarubicin, doxorubicin and vincristine, and exhibiting a highest negative correlation with multiple drug resistance (MDR)-linked gene expression, may be the best choice of treatment for the studied OSCC patients [119]. Kim et al showed that the incorporation of paclitaxel into exosomes significantly augmented paclitaxel accumulation in drug-resistant lung cancer cells and was 50 times more cytotoxic than conventional paclitaxel in vitro [116].…”

Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents

“…The group of HNSCC is the sixth most frequent cancer worldwide, with a global incidence of more than half a million annual cases [ 3 ] and about 65,000 of new cases only in the United States in 2019 [ 10 ], and it is highly resistant to a wide range of structurally different drugs with diverse cytotoxic mechanisms of action [ 3 ]. Indeed, the efficacy of pharmacological treatment is limited as patients acquire drug resistance, showing poor response to chemotherapeutics and therefore pushing physicians to use radiations and surgical interventions that often lead to a permanent impairment of oral functions [ 11 , 12 ]. Thus, despite many drugs have demonstrated promising ability, the development of new therapeutic options is still urgently needed.…”