Browsing by Author "Shields, Misty D."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Adenocarcinoma Harboring EGFR-RAD51 Fusion Treated with Osimertinib: A Case Report
    (Elsevier, 2024-04) Lai, Sunny Y.; Richardson, Noah H.; Tran, Mya; Hanna, Nasser H.; Shields, Misty D.; Medicine, School of Medicine
    EGFR mutations are among the most common driver mutations in lung adenocarcinoma. Rare alterations, such as the EGFR-RAD51 fusion, respond to treatment with EGFR tyrosine kinase inhibitors but can be missed by limited genomic sequencing panels. Here, we report a case of metastatic lung adenocarcinoma in a never-smoker patient who initially did not have a targetable alteration identified on two different sequencing panels. The initial response to combination chemoimmunotherapy was short-lived. A rare EGFR-RAD51 fusion was then identified using a more in-depth sequencing panel. The patient experienced a dramatic and durable response to osimertinib. This case highlights the rarity of EGFR-RAD51 fusions, the efficacy of EGFR tyrosine kinase inhibitors, and the importance of a thorough search for targetable alterations in never-smokers with lung adenocarcinoma.
  • Thumbnail Image
    Item
    Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer
    (Elsevier, 2024) Chakraborty, Subhamoy; Sen, Utsav; Ventura, Kedwin; Jethalia, Vrinda; Coleman, Charles; Sridhar, Subhasree; Banerjee, Avisek; Ozakinci, Hilal; Mahendravarman, Yazhini; Snioch, Konrad; de Stanchina, Elisa; Shields, Misty D.; Tomalin, Lewis E.; Demircioglu, Deniz; Boyle, Theresa A.; Tocheva, Anna; Hasson, Dan; Sen, Triparna; Medicine, School of Medicine
    Lurbinectedin is an approved second-line treatment for small-cell lung cancer (SCLC). SCLC clinical trials combining lurbinectedin with PD-L1 blockade are currently ongoing. However, the immunomodulatory effects of lurbinectedin remain largely unknown. In this study, we demonstrate that lurbinectedin treatment activates the STING pathway, which increases interferon (IFN) signaling, pro-inflammatory chemokines, and major histocompatibility complex class I (MHC-I) in SCLC models. Lurbinectedin treatment augments the anti-tumor immune response of PD-L1 blockade with significant tumor regression in first-line and maintenance settings in SCLC mouse models. In vivo, lurbinectedin treatment increases CD8+ T cells and M1 macrophages and decreases immunosuppressive M2 macrophages. STING and CD8 depletion reverses the anti-tumor response. Interestingly, our study shows that lurbinectedin treatment upregulates MHC-I/II genes and CD8 in SCLC clinical samples. We provide mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and demonstrate that lurbinectedin treatment represents a promising therapeutic strategy to potentiate the efficacy of immunotherapy in SCLC.