Abstract 5260: Preclinical studies with ONC201 in combination with clinically approved chemotherapy as a novel treatment strategy against Small Cell Lung Cancer (SCLC)

Abstract

Abstract According to the American Cancer Society, about 10-15 percent of all lung cancer diagnoses are small cell lung cancer (SCLC). The median survival rate of limited-stage small cell lung cancer is about 12 to 16 months. Several clinically approved chemotherapy drugs have been used to treat SCLC, with several more currently under clinical trials. However, a novel combination is still needed to increase patient life expectancy. ONC201 is an impridone, currently in clinical trials, that has proven to have proapoptotic effects in multiple tumor types. We hypothesized that treating SCLC cell lines with ONC201 in conjunction with clinically approved chemotherapy drugs, such as etoposide and carboplatin, will have a synergistic effect and serve as a potential novel combination treatment plan. SCLC cell lines H1048 and H1105 were treated for 72 hours with ONC201 and etoposide, or ONC201 and carboplatin. CellTiter-Glo cell viability assay and Western blotting of PARP cleavage and ATF4 were used to check synergy in the combination treatments. The combination of ONC201 and clinically approved chemotherapy drugs, etoposide and carboplatin, revealed that there was an upregulation in cleaved PARP and a synergistic effect on the overall cell samples. When looking at the combination index of the cell proliferation assays, the best index for each combination was 0.867 with an ONC201 dosage of 4 μM and an etoposide dosage of 0.05 μg/mL in H1048, 0.43191 at ONC201 dosage 0.3125 μM and etoposide dosage 2.5 μg/mL in H1105, and 0.20278 at ONC201 dosage 2.5 μM and carboplatin dosage 3.125 μg/mL in H1105. We are currently testing drug combinations including a triple drug combination of ONC201 and two clinically approved drugs and studying the mechanism underlying the synergies, with the potential to translate this novel combination treatment plan of ONC201 and clinically approved drugs into a clinical regimen to improve the outcome of SCLC patients. Citation Format: Young S. Lee, Lanlan Zhou, Christopher Azzoli, Wafik S. El-Deiry. Preclinical studies with ONC201 in combination with clinically approved chemotherapy as a novel treatment strategy against Small Cell Lung Cancer (SCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5260.