Investigation of Synergistic Combinations of Chemotherapy Drugs for the Treatment of Oral Cancer

Abstract

Oral cancer is one of the most common forms of cancer among developing countries but despite current efforts, the survival of oral cancer has remained constant. Current research on oral cancer is centered on clinical studies focused on single drugs or very few combinations of the most common therapeutics historically used to treat oral cancer. However, there is a major gap in the literature about combinations of drug treatments for oral cancer. The goal of this study is to explore combination treatments and assess whether any synergistic effects can be produced. To accomplish this, two oral squamous cell carcinoma (OSCC) cell lines, Cal‐27 and OECM‐1 from the tongue and the oral cavity, respectively, will be used to investigate the efficacy of single drugs as well as combinations of drugs from a wide array of chemotherapy agents currently used to treat oral cancer as well as other forms of cancer. Thus far, Cell Titer Glo assays have been performed in triplicate for both Cal‐27 and OECM‐1 to analyze their viability in the presence of four drugs used to treat other forms of cancer with different mechanisms of action: PD0, a MEK inhibitor, IBET‐762, a BET inhibitor, ABT‐199, a Bcl‐2 inhibitor, and JQ1, a BRD4 inhibitor. GI50 values were gathered from each assay. Cal‐27 presented higher GI50 values than OECM‐1 for IBET‐762 and JQ1 at 1.52 mM and 1.64 mM, respectively. The GI50 values for OECM‐1 treatment with IBET‐762 and JQ1 were lower at 1.07 mM and 1.21 mM, respectively. Both cell lines were found to have similar resistance to PD0, around 1.05 mM, and ABT‐199, around 1.02 mM. High GI50 values across the cell lines indicate that both Cal‐27 and OECM‐1 are resistant to the four drugs that were tested. In the future, Cal‐27 and OECM‐1 will be treated with a panel of 10 drugs currently used clinically to treat oral cancer to gather baseline data to understand how these cell lines react to current treatment. The drugs that will be used include: Cisplatin, 5‐FU, Taxol, Docetaxel, Hydroxyurea, Methotrexate, Bleomycin, Gemcitabine, and Vincristine, all of which interfere with DNA synthesis and cell growth. Then, Cal‐27 and OECM‐1 will be treated with new combinations of drugs currently used to treat oral cancer and drugs not currently used for oral cancer but used to treat other forms of cancer. Some of these drugs include: Gefitinib, a EGFR inhibitor, Venetoclax, a BCL‐2 inhibitor, Irinotecan, a topoisomerase inhibitor, Mitoxantrone, a topoisomerase 2 and PKC inhibitor, and several other drugs. Cellular responses will then be assessed to determine if any combinations are synergistic. The data generated can aid researchers in understanding how different OSCC cells respond to drug combinations, which may lead to more successful clinical treatment options in the future.