PDLIM2 Therapy for Cancer
University of Pittsburgh researchers have developed a method to restore PDLIM2 expression and/or function in tumor- and tumor-associated cells, which promotes antitumor activity and synergizes with anti-PD-1 therapy. In combination with chemotherapy and anti-PD-1 therapy, restoration of PDLIM2 has demonstrated complete remission of most lung cancers, establishing a new foundation for PDLIM2-based combination therapies for cancer treatment. Additionally, PDLIM2 expression and function in tumor cells can be used as a marker to assess cancer risk, diagnosis, prognosis and treatment response.
Description
PDLIM2 is a protein that acts as a tumor suppressor and whose expression is often repressed in various cancers. Repression of PDLIM2 is linked to cancer development, progression, metastasis, and therapy resistance, including complete resistance to anti-PD-1 therapy and epigenetic drugs. T cells are one of the body’s first lines of defense against foreign cells, including cancer cells. The interaction between the protein PD-1 on T cells and its ligand PDL-1 helps to mediate the immune response by prohibiting T cell-mediated killing, crucial for preventing an out-of-control immune response, but which can also prohibit effective killing of cancer cells which express PD-L1. Anti-PD-1/PD-L1 immunotherapy aims to block the PD-1/PDL-1 interaction, however, many cancers are resistant to this treatment.Applications
• Component of combination cancer therapy• Sensitizes therapy-resistant cancers
• Biomarker for cancer risk and response to treatment
Advantages
• Overcomes a common barrier to effective immunotherapy treatment• Demonstrates tumor specificity and low toxicity
Invention Readiness
In vivo dataIP Status
https://patents.google.com/patent/US20220135634A1Related Publication(s)
Sun, F., Li, L., Yan, P. et al. Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance. Nat Commun 10, 5324 (2019). https://doi.org/10.1038/s41467-019-13331-x
Li, L. Sun, F., Han, L. et al. PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis. JCI Insight. 6:e144394 (2021). https://doi.org/10.1172/jci.insight.144394