The Therapeutic Role of lncRNA-Mediated DNA Repair in Lung Cancer
Abstract
The purpose of the proposal was to determine the role LINC00261 plays in mediating cellular response to DNA damage in lung cancer. Scope of work was designed to test the mechanistic role of LINC00261 in effecting DNA repair through NER pathway, the effect LINC00261 has on total mutational burden and subsequent presentation of neoantigens, and whether the presence of LINC00261 affects sensitivity of lung cancer to small molecule therapeutics targeting DNA repair (olaparib) or activity of pembrolizumab (anti-PD-L1) to optimize application of neoadjuvant therapy. Interim results for Aim 2 indicate that LINC00261 expression levels are elevated under interferon gamma-mediated immune stimulation, and that the presence of LINC00261 enhances activation of MHC Class II presentation markers; indicating that LINC00261 may serve as a surrogate for high neoantigen load and a complementary biomarker to PD-L1 expression for effective immunotherapy. Less progress has been made on Aims 1 and 3; Aim 1 progress demonstrated that the S1m strategy for identifying LINC00261 binding partners has failed. Approved alt. strategies are being pursued. Aim 3 regulatory approvals are obtained.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2022
- Accession Number
- AD1180408
Entities
People
- Crystal N Marconett
- Evan Mihalakakos
- Jonathan Castillo
- Michele R. Correa
Organizations
- University of Southern California