MCL1

Overview

MCL1 is an anti-apoptotic BCL-2 family protein that promotes cell survival by sequestering pro-apoptotic BH3-only proteins. Upregulation of MCL1 is a mechanism of chemoresistance observed across cancer types. In the HGSOC precursor lesion context, MCL1 upregulation is part of the interferon-related DNA damage resistance signature (IRDS).

Alterations observed in the corpus

  • Anti-apoptotic BCL-2 family member upregulated as part of the interferon-related DNA damage resistance signature (IRDS) in serous tubal intraepithelial carcinoma stage C (STIC.C) and cancer epithelial cells in high-grade serous ovarian carcinoma (HGSOC) precursors; upregulation appears at the STIC.C stage PMID:39386723.
  • MCL1 identified as a significantly mutated gene in pan-lung cancer TCGA analysis (n=1144) with somatic alterations observed across lung adenocarcinoma and squamous cell carcinoma subtypes PMID:27158780
  • Alteration identified as part of the actionable alteration list in cisplatin-resistant germ cell tumors (GCT) PMID:27646943
  • MCL1 overexpression detected in osteosarcoma (OS) in a pediatric precision-oncology cohort; identified alongside MYC and CCNE1 as BET- and CDK4/6-inhibitor targets in the same patient PMID:28007021

Cancer types (linked)

  • High-grade serous ovarian carcinoma (HGSOC) precursors (STIC) — MCL1 upregulation as part of the IRDS in STIC.C and cancer; may contribute to chemoresistance observed in >80% of stage III/IV HGSOC PMID:39386723.

Co-occurrence and mutual exclusivity

  • Co-upregulated with MX1 and other IFN-stimulated genes as part of the IRDS signature in STIC.C and cancer epithelial cells PMID:39386723.

Therapeutic relevance

  • IRDS-associated MCL1 upregulation may contribute to the chemoresistance (platinum/taxane) observed in advanced HGSOC; MCL1 inhibitors are in clinical development PMID:39386723.

Open questions

  • Whether MCL1 upregulation in STIC.C is causally linked to clinical chemoresistance or is correlative requires prospective validation.
  • Direct MCL1 inhibitor strategies in HGSOC have not been evaluated in this corpus.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27646943

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15.