Inhibition of RET Proto-Oncogene as Novel Immune-Based Strategy Against SCLC
Abstract
Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer and is defined by neuroendocrine features, high rate of metastasis, and strong association with smoking. SCLC patient respond to chemotherapy at first, however, relapse quickly with acquired resistance to other chemotherapies. Even the immune checkpoint inhibitors have shown only marginal benefits in SCLC patients. Therefore, there is an utmost need to develop novel therapeutic agents against this deadly subtype of lung cancer. Screening of patient samples has identified mutation in REaranged during Transfection (RET) gene linked to SCLC pathogenesis. However, its clinical significance in SCLC has not been studied yet. Here, we are analyzing the ability of Pralsetinib, a highly potent and selective inhibitor of RET, to inhibit SCLC in pre-clinical mouse models of SCLC. RET signaling in monocytes has been shown to increase the expression of chemokine and cytokines associated with myeloid-derived suppressor cells (MDSCs). Tumors are known to recruit MDSCs to inhibit anti-tumor immune response and dampen immunotherapy response. We will also analyze the ability of Pralsetinib to activate anti-tumor immune responses and enhance the efficacy of immunotherapy against SCLC by suppressing MDSCs. Overall, these studies will help in establishing the preclinical significance of Pralsetinib against SCLC.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1225482
Entities
People
- Dinesh K. Ahirwar
Organizations
- Indian Institute of Technology Jodhpur