FBXO7

Overview

FBXO7 (F-box only protein 7) is a substrate recognition subunit of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex. Copy number loss of FBXO7 is observed in colorectal cancer and is associated with chromosomal instability (CIN) and poor outcomes. FBXO7 loss has been identified as a synthetic lethal vulnerability exploitable via CHEK1 inhibition.

Alterations observed in the corpus

  • Copy number loss (shallow deletion) in 32.5% of CRC; associated with reduced expression, CIN, and poor outcomes; identified as the target gene for synthetic lethality (SL) exploitation via CHEK1 inhibition PMID:36334560

Cancer types (linked)

  • CRC: copy number loss in 32.5% of cases; associated with CIN and reduced overall survival PMID:36334560

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • FBXO7-deficient CRC cells are synthetically lethal to CHEK1 inhibition (siRNA or prexasertib); provides rationale for CHEK1 inhibitor use in FBXO7-deleted CRC PMID:36334560

Open questions

  • Whether FBXO7 copy number loss is a reliable biomarker for prexasertib patient selection requires prospective validation.

Sources

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