Lung cancer stem cell (LCSC) regulatory pathways (LCSC pathways)

Lung cancer stem cell (LCSC) regulatory pathways encompass a network of evolutionary conserved signaling cascades, most notably Wnt/beta-catenin, Notch, and Hedgehog, that govern the maintenance, self-renewal, and pluripotency of a subpopulation of tumor-initiating cells (Lau et al., 2017). These pathways are frequently dysregulated in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), where they drive tumor heterogeneity, metastasis, and the development of resistance to conventional chemotherapy and radiotherapy (Sullivan et al., 2010). LCSCs are typically identified by specific markers such as CD133, CD44, and high aldehyde dehydrogenase (ALDH) activity, which correlate with poor clinical outcomes and disease recurrence (MacDonagh et al., 2017). Therapeutic strategies targeting these pathways, using agents like Hedgehog inhibitors (e.g., vismodegib) or Notch-targeting antibodies, aim to eradicate the quiescent stem cell population that survives standard treatments (Zakaria et al., 2017). However, the clinical application of these inhibitors is often limited by significant systemic toxicities, as these pathways are also essential for the homeostasis and regeneration of normal adult stem cells in the gut, skin, and bone marrow (Takebe et al., 2015). Current research is focused on identifying LCSC-specific vulnerabilities and combination therapies to improve the therapeutic window and prevent relapse.

Other names

Lung cancer stem cell signalingLCSC maintenance pathwaysStemness pathways in lung cancerLung tumor-initiating cell pathways

Inhibition of developmental signaling cascades (Wnt, Notch, Hedgehog) to deplete the cancer stem cell pool, induce differentiation, and reverse chemoresistance (Takebe et al., 2015).