Abstract 4979: Evaluation of heme inhibitory therapy in combination with radiation of lung cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.4979-4979
• Main Authors: Salamat, Narges, Wang, Tianyuan, Berisha, Eranda, Castro, Maria Del Carmen Chacon, Ashrafi, Adnin, Saha, Debabrata, Mason, Ralph P., Liu, Li, Zhang, Li
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-4979

Lung cancer is the leading cause of cancer-related death in the United States, with a 5-year survival rate of less than 25%. While most lung cancer patients receive radiation therapy, radioresistance severely impacts treatment outcomes. Thus, development of therapeutics to potentiate durable response to radiation therapy may be key to improving treatment outcomes. Research in our lab has previously implicated heme, a central biosynthetic molecule with important functions in diverse molecular and cellular processes, in lung cancer development and progression. To target heme, we designed heme-sequestering protein 2 (HeSP2) which displays potent anti-tumor activity in mouse tumor models. By decreasing tumor metabolic demand through heme sequestration, HeSP2 can significantly alleviate tumor hypoxia, a dominant radioresistance mechanism. Tumor hypoxia correlates with poor clinical outcomes by acting via multiple mechanisms such as inhibiting radiation-induced DNA damage and inducing the HIF-1 pathway that leads to antioxidant generation. Here, our preliminary data show that HeSP2 potentiates the antitumor efficacy of ionizing radiation. To see the effect of HeSP2 in combination with radiotherapy, in summary we subcutaneously implanted A549-luc, NSCLC cell lines with mutation in Kras and KLB1 in SCID mice. After 1-2 weeks mice were treated with saline (Control), HeSP2(25 mg/kg, i.v, twice a week), radiation (5 Gray, once per week at week 2 and 3), and HeSP2 combined with radiation (25 mg/kg, i.v, twice a week plus 5 Gray, once per week at week 2 and 3. Tumor tissues were harvested, processed and paraffin embedded for immunohistochemistry (IHC). Preliminary results indicate HeSP2 in combination with radiation reduce the levels of multiple angiogenic markers and vascular markers as well as microvessel density. These results indicate that heme sequestration in combination with radiation can be an effective strategy for suppressing lung tumors. Citation Format: Narges Salamat, Tianyuan Wang, Eranda Berisha, Maria Del Carmen Chacon Castro, Adnin Ashrafi, Debabrata Saha, Ralph P. Mason, Li Liu, Li Zhang. Evaluation of heme inhibitory therapy in combination with radiation of 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 4979.