Blocking the functional domain of TIP1 by antibodies sensitizes cancer to radiation therapy

Biomed Pharmacother. 2023 Aug 23;166:115341. doi: 10.1016/j.biopha.2023.115341. Online ahead of print.ABSTRACTNon-small-cell lung cancer (NSCLC) and glioblastoma (GB) have poor prognoses. Discovery of new molecular targets is needed to improve therapy. Tax interacting protein 1 (TIP1), which plays a role in cancer progression, is overexpressed and radiation-inducible in NSCLC and GB. We evaluated the effect of an anti-TIP1 antibody alone and in combination with ionizing radiation (XRT) on NSCLC and GB in vitro and in vivo. NSCLC and GB cells were treated with anti-TIP1 antibodies and evaluated for proliferation, colony formation, endocytosis, and cell death. The efficacy of anti-TIP1 antibodies in combination with XRT on tumor growth was measured in mouse models of NSCLC and GB. mRNA sequencing was performed to understand the molecular mechanisms involved in the action of anti-TIP1 antibodies. We found that targeting the functional domain of TIP1 leads to endocytosis of the anti-TIP1 antibody followed by reduced proliferation and increased apoptosis-mediated cell death. Anti-TIP1 antibodies bound specifically (with high affinity) to cancer cells and synergized with XRT to significantly increase cytotoxicity in vitro and reduce tumor growth in mouse models of NSCLC and GB. Importantly, downregulation of cancer survival signaling pathways was found in vitro and in vivo following treatment with anti-TIP1 antibodies. TIP1 is a new therapeutic target for cancer treatment. Antibodi...

Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - August 25, 2023 Category: Drugs & Pharmacology Authors: Abhay K Singh David Ya Dadey Michael J Rau James Fitzpatrick Harendra K Shah Minakshi Saikia Reid Townsend Dinesh Thotala Dennis E Hallahan Vaishali Kapoor Source Type: research