DLL3 regulates Notch signaling in small cell lung cancer
Year: 2022
Type: article
Abstract: Tumor heterogeneity plays a critical role in tumor development and response to treatment. In small-cell lung cancer (SCLC), intratumoral heterogeneity is driven in part by the Notch signaling pathway, which reprograms neuroendocrine cancer cells to a less/non-neuroendocrine state. Here we investigated the atypical Notch ligand DLL3 as a biomarker of the neuroendocrine state and a regulator of cell-cell interactions in SCLC. We first built a mathematical model to predict the impact of DLL3 expression on SCLC cell populations. We next tested this model using a single-chain variable fragment (scFv) to track DLL3 expression in vivo and a new mouse model of SCLC with inducible expression of DLL3 in SCLC tumors. We found that high levels of DLL3 promote the expansion of a SCLC cell population with lower expression levels of both neuroendocrine and non-neuroendocrine markers. This work may influence how DLL3-targeting therapies are used in SCLC patients.
Source: iScience
Authors: Jun W. Kim, Julie H. Ko, Julien Sage
Institution: Stanford University
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Awards: G2168804857, G2424621651, G2674442865, Phenotype Heterogeneity and Dynamics in SCLC, G6553593135, G6559991919, Novel therapeutic approaches for enhancing anti-tumor immunity in SCLC, G7379403236, G8182187627, Molecular mechanisms of SCLC initiation and detection in mice and humans, G9000043295, G9000112467
OpenAlex ID: W4309344675