Abstract 1476: FOXM1 inhibition: A novel therapeutic approach for small cell lung cancer

Abstract

Abstract Outcomes from small cell lung cancer (SCLC) are dismal. Most SCLC patients have distant metastasis at diagnosis and the 5-year survival of these patients is around 2.8%. Despite initial response to chemotherapy and immunotherapy, relapses are very common. No targeted therapy is available for SCLC. Thus, there is an urgent need to understand the acquisition of chemoresistance, and to identify novel targets and therapeutic strategies for this deadly disease. Recently, FOXM1 was identified as an essential component in SCLC tumor growth. Our aim is to develop FOXM1-targeted therapy to thwart SCLC progression and the development of chemoresistance. We have targeted FOXM1 using highly specific small molecule inhibitor FDI-6 and found that FOXM1 inhibition drastically reduces colony formation and cell migratory capabilities in multiple SCLC cell lines (SBC3, SBC5). Additionally, we observed that FOXM1 downregulation via FDI-6 reduced SCLC growth both as monotherapy and in combination with cisplatin. Based on these studies, we conclude that FOXM1 inhibition alone or in combination with cisplatin could be a unique therapeutic approach for SCLC. Citation Format: Md Arafat Khan, Parvez Khan, Mahek Fatima, Asad Ur Rehman, Shailendra Kumar Maurya, Sameer Mohiuddin, Ramakanth Chirravuri Venkata, Jesse L. Cox, Sung Hoon Kim, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Apar K. Ganti, Surinder K. Batra, Mohd Wasim Nasser. FOXM1 inhibition: A novel therapeutic approach for small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1476.