HES1

Overview

HES1 (Hes Family BHLH Transcription Factor 1) is a canonical downstream target of NOTCH signaling. In small cell lung cancer (SCLC), HES1 upregulation upon Notch activation suppresses neuroendocrine differentiation, consistent with the tumor-suppressive role of Notch signaling in SCLC.

Alterations observed in the corpus

• Upregulated upon Notch activation in SCLC mouse models; consistent with canonical Notch target activation suppressing neuroendocrine differentiation; defines the non-neuroendocrine SCLC transcriptional subtype PMID:26168399

Cancer types (linked)

• SCLC: Expression marker of the non-neuroendocrine SCLC transcriptional subtype; upregulated by Notch pathway activation in mouse models; Notch/HES1 activation suppresses SCLC initiation and prolongs survival in TKO mice PMID:26168399

Co-occurrence and mutual exclusivity

• Inversely correlated with neuroendocrine markers ASCL1, DLK1, CHGA, GRP, SYP, NCAM1 in SCLC transcriptional subtypes PMID:26168399

Therapeutic relevance

• Notch pathway agonism (leading to HES1 upregulation) is proposed as a therapeutic strategy in SCLC, though clinically tractable Notch-activating agents and patient-selection biomarkers remain to be defined PMID:26168399

Open questions

• Clinically tractable Notch-activating agents and patient-selection biomarkers for Notch/HES1-based therapies in SCLC remain undefined PMID:26168399

Sources

• PMID:26168399

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