Emerging evidence for CHFR as a cancer biomarker: from tumor biology to precision medicine

Abstract

Novel insights in the biology of cancer have switched the paradigm of a "one-size-fits-all" cancer treatment to an individualized biology-driven treatment approach. In recent years, a diversity of biomarkers and targeted therapies has been discovered. Although these examples accentuate the promise of personalized cancer treatment, for most cancers and cancer subgroups no biomarkers and effective targeted therapy are available. The great majority of patients still receive unselected standard therapies with no use of their individual molecular characteristics. Better knowledge about the underlying tumor biology will lead the way toward personalized cancer treatment. In this review, we summarize the evidence for a promising cancer biomarker: checkpoint with forkhead and ring finger domains (CHFR). CHFR is a mitotic checkpoint and tumor suppressor gene, which is inactivated in a diverse group of solid malignancies, mostly by promoter CpG island methylation. CHFR inactivation has shown to be an indicator of poor prognosis and sensitivity to taxane-based chemotherapy. Here we summarize the current knowledge of altered CHFR expression in cancer, the impact on tumor biology and implications for personalized cancer treatment.

Fig. 1

CHFR delays entry into metaphase in respons to microtubular stress by effecting target proteins in a proteosome-dependent and a proteosome-independent manner

Fig. 2

CHFR gene and protein. Schematic representation of promoter CpG island methylation, mutation and polymorphisms with functional significance. of a CHFR gene encompassing 18 exons. CpG island is enlarged with CpG dinucleotides as vertical lines. TSS: transcription start site * mutation. # polymorphism. b CHFR protein consisting of 664 aminoacids. FHA: forhead-associated domain. RING: ringfinger domain. CR: cysteine-rich domain. PBZ: RAR-binding zinc-finger domain. Mutations in black, polymorphism in red