Melanoma-associated antigen expression and the efficacy of tyrosine kinase inhibitors in head and neck cancer

Abstract

Abstract. Melanoma-associated antigen (MAGE) has been identified in a variety of types of cancer. The expression of several MAGE subgroups is correlated with poor prognosis and chemotherapeutic resistance. One target of chemotherapeutic treatment in head and neck cancer is the epidermal growth factor receptor (EGFR). The efficacy of tyrosine kinase inhibitors (TKI) in the context of melanoma-associated antigens is discussed in the present study. Five human squamous cell carcinoma cell lines were treated with the EGFR TKIs, erlotinib and gefitinib. The efficacy of these agents was measured using a crystal violet assay. Furthermore, the expression levels of MAGE-A1, -A5, -A8, -A9, -A11 and -A12 were determined by reverse transcription-quantitative polymerase chain reaction. The association between TKI efficacy and MAGE-A expression was analyzed by linear regression. The cell lines revealed inhomogeneous expression patterns for the MAGE-A subgroups. Four of the five cell lines demonstrated a good response to erlotinib and gefitinib. However, treatment with erlotinib induced better results than those of gefitinib, and revealed a concentration-dependent effect. The expression of MAGE-A5 and -A11 were significantly correlated with lower efficacy of erlotinib and gefitinib. By contrast, MAGE-A12 was associated with a superior response to these two drugs. One cell line, which expressed all investigated MAGE-A subgroups, was entirely resistant to the two TKIs. These results revealed a notable correlation between MAGE-A5 and -A11 and lower efficacy of EGFR TKIs. Pretreatment analysis of MAGE-A status may therefore aid improvement of chemoprevention using erlotinib and gefitinib in head and neck cancer.

Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

“…Furthermore, this finding has also been confirmed for erlotinib and gefitinib (25). Notably, comparable to our previous results in cell culture, the MAGE-A11 expression in the TMAs was only modest (25). However, its expression can likely be used to separate patients with a higher risk from those with a lower risk.…”

“…In addition, we have previously provided strong evidence that MAGE-A11 is correlated with the reduced effects of numerous agents commonly used for the treatment of head and neck cancer, such as cisplatin, 5-fluorouracil, docetaxel, paclitaxel, cetuximab and panitumumab (9,10). Furthermore, this finding has also been confirmed for erlotinib and gefitinib (25). Notably, comparable to our previous results in cell culture, the MAGE-A11 expression in the TMAs was only modest (25).…”

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

“…Although various cancers demonstrate MAGE-A family gene overexpression and the accumulation of their encoded proteins [19][20][21][22][23][24][25][26][27][28], the specific MAGE-A gene products that…”

“…Although various cancers demonstrate MAGE-A family gene overexpression and the accumulation of their encoded proteins [19][20][21][22][23][24][25][26][27][28], the specific MAGE-A gene products that are functionally relevant in breast cancer remain largely undetermined. To address this, we first analyzed the RNA-seq data of 70 breast cancer cell lines to determine the breast-cancer-related expression patterns of the MAGE-A gene family members.…”

“…Indeed, it was reported that different members of the MAGE-A gene family are upregulated in various types of cancers [19][20][21][22][23][24][25][26][27][28]. For example, MAGEA1 is upregulated in lung cancer, melanoma, and gastric cancer; MAGEA3 is upregulated in breast and lung cancer; MAGEA4 is upregulated in melanoma; MAGEA5 is upregulated in head and neck cancer; and MAGEA9 is upregulated in liver and colon cancer.…”