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G protein-coupled receptor, family C, group 5 member A (GPRC5A) is a retinoid-inducible protein, which has been characterized as a tumor-suppressor gene in lung cancer. The present study further examined GPRC5A expression in non-small cell lung cancer (NSCLC) for any association with the clinical features and treatment outcomes of patients with NSCLC. A total of 30 paired NSCLC tumor and adjacent normal tissues were analyzed for the detection of GPRC5A mRNA and protein using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Immunohistochemistry was performed to determine the GPRC5A expression levels in 110 NSCLC and 60 para-tumor tissues. The results confirmed significantly lower expression levels of GPRC5A in NSCLC tumors compared with the corresponding noncancerous tissues (P<0.001). Lost GPRC5A expression was significantly associated with the tumor histological type (P=0.008), poor tumor differentiation (P<0.001) and tumor-node-metastasis (TNM) stage (P<0.001). Kaplan-Meier curve analysis revealed that patients with NSCLC with low GPRC5A expression tumors had a worse prognosis compared with those with high GPRC5A expression tumors (P=0.010). The results of multivariate Cox analysis further suggested that low GPRC5A expression was an independent prognostic factor for patients with NSCLC (P<0.001). The results of this study suggest GPRC5A expression has clinical potential as a prognostic biomarker for patients with NSCLC. [ABSTRACT FROM AUTHOR]

For advanced non-small-cell lung cancer (NSCLC) with mutations to the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors, including erlotinib are indicated for the first-line treatment. Liver injury is one of the multiple adverse effects of erlotinib and may affect its safety. The present study investigated the mechanism of erlotinib-induced hepatotoxicity in vitro and provided experimental evidence for the screening of potential hepatoprotectors. Erlotinib induced dose-dependent cytotoxicity in human L-02 hepatic cells 72 h after treatment. In other experiments, L-02 cells were treated with erlotinib for 48 h and thereafter exhibited typical features of apoptosis. Erlotinib caused alterations to nuclear morphology, including chromatin condensation and karyopyknosis; it also increased the fraction of late apoptotic cells and regulated apoptotic protein levels, activating caspase-3 and cleaving of poly-ADP-ribose polymerase. Furthermore, 48 h exposure to erlotinib disturbed mitochondrial function by decreasing the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-associated X proteins and reducing mitochondrial membrane potential. The results of this in vitro study indicate that erlotinib-induced hepatotoxicity may occur through mitochondrial-pathway-mediated apoptosis [ABSTRACT FROM AUTHOR]

Gefitinib has come to be the most widely used epidermal growth factor receptor-tyrosine kinase inhibitor in the treatment of advanced non-small cell lung cancer (NSCLC) in Asian patients. Common side effects include mild to moderate skin rash and diarrhea, however, drug-induced liver injury of varying severity is overlooked in long-term gefitinib administration and rarely reported. The current case report presents a female Chinese NSCLC patient who developed severe gefitinib-induced hepatotoxicity and was rechallenged with gefitinib following a 3-month break. The patient achieved partial clinical remission but developed drug-induced grade 4 hepatotoxicity following gefitinib administration for 14 months. As an alternative, 4 cycles of chemotherapy were administered to control tumor progression. Following restoration of the patient's liver function, gefitinib was rechallenged together with active hepatoprotective therapy. The patient presented good disease control and maintained normal liver function for >6 months. Thus, sequential chemotherapy and gefitinib rechallenge with hepatoprotective therapy may be a potential new treatment strategy for gefitinib-induced hepatotoxicity.