Abstract 289: B7-H3 mediated metabolic reprogramming promotes small cell lung cancer progression

Abstract

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Small cell lung cancer (SCLC) is an aggressive subtype of lung cancer. The overall survival rate of SCLC is dismal owing to early metastasis, chemoresistance, higher rate of recurrence, and lack of available treatment options. Although some immunotherapeutic drugs have been approved for SCLC, they are effective only in a small fraction of the patient population. This necessitates the quest to find promising vulnerabilities against SCLC. Bioinformatic analysis on SCLC data set in the backdrop of various immune checkpoint regulators revealed B7-H3 as a promising target. The bioinformatics data was recapitulated in SCLC cell lines and human SCLC tissues. To delineate the effects of B7-H3 targeting, we performed CRISPR-Cas9 mediated B7-H3 knockout in SCLC cell lines. B7-H3 knockout in SCLC cells showed a decrease in colony formation, migration, and wound healing properties. Our results suggest that deletion of B7-H3 decrease the functional activities and activation of oncogenic signaling pathways, such as Erk, Akt, and Stat3. Further, we assessed if B7-H3 regulates SCLC metabolism. Preliminary data showed that B7-H3 knockout in SCLC cells inhibits glucose uptake, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR), suggesting its role in SCLC metabolic reprogramming. Altogether, our data indicate that B7-H3 plays a crucial role in SCLC pathogenesis and could serve as a potential therapeutic target for SCLC. Citation Format: Mahek Fatima, Parvez Khan, Asad Ur Rehman, Md Arafat Khan, Shailendra Kumar Maurya, Aatiya Ahmad, Mohd Ali Zaidi, Shailendra Gautam, Subodh Lele, Surinder Kumar Batra, Mohd Wasim Nasser. B7-H3 mediated metabolic reprogramming promotes small cell lung cancer progression [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 289.