Casein Kinase-1 Epsilon as a Novel Therapeutic Target Against Small Cell Lung Cancer
Abstract
Although SCLC patients respond to initial chemotherapies, most of them will inevitably relapse, resulting in early death. High incidence of metastasis and drug resistance are the major factors responsible for reduced survival observed in SCLC patients compared to other type of lung cancers. In this regard, we are analyzing the therapeutic utility of Umbralisib in transgenic and patient-derived xenograft mouse models of SCLC. Umbralisib is a dual Phosphatidylinositol-3-kinase (PI3K) and caseinkinase-1 (CK1) inhibitor. PI3K and CK1 are dysregulated in SCLC and are known to drive translation of various oncogenes, including MYC, which is involved in SCLC progression and drug resistance. We hypothesize that a clinically approved Umbralisib may inhibit SCLC progressing and metastasis by suppressing various oncogenic activities. In this proposal, we will evaluate the ability of Umbralisib to prevent or delay the malignant transformation of the lungs and subsequent progression/metastasis in a transgenic and patient derived-xenograft mouse model of SCLC. We will further analyze if Umbralisib can inhibit MYC signaling and act synergistically with chemotherapy against aggressive and metastatic SCLC. These studies will establish the therapeutic potential of Umbralisib against SCLC progression, metastasis and drug resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1212269
Entities
People
- Ashok Kumar
- Dinesh K. Ahirwar
Organizations
- Indian Institute of Technology Jodhpur