bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2023‒10‒22
five papers selected by
Lara Paracchini, Humanitas Research

  1. Nat Commun. 2023 Oct 16. 14(1): 6505
      High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.
  2. Int J Cancer. 2023 Oct 20.
      Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases  = 27, ncontrols  = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases  = 29, ncontrols  = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.
    Keywords:  cell-free DNA; diagnosis; methylation; ovarian cancer
  3. JCO Oncol Pract. 2023 Oct 18. OP2300260
      A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses. Additionally, we discuss a proposed professional expansion of the oncology practice relating to the diagnostic workup of individuals found to have an MCED signal positive for cancer. As MCED blood tests have the potential to dramatically upend current cancer screening paradigms and downstream cancer therapy, it is imperative for oncologists to be aware of important clinical studies and the multitude of unanswered questions. The current gaps in the clinical implication of these tests may serve as a meaningful and rewarding expansion of oncology practice.
  4. Clin Epigenetics. 2023 Oct 18. 15(1): 165
      BACKGROUND: Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor overall survival, with only 30% of patients surviving for longer than 5 years after diagnosis. The reason for this poor outcome includes late diagnosis due to non-specific symptoms and a lack of any highly effective biomarkers of the early stages of ovarian carcinogenesis. However, it is important to note that some modifiable lifestyle factors can be preventative [pregnancy, breastfeeding and combined oral contraceptives pill (COCP) use].RESULTS: There is now increasing data reporting the role of epigenetic changes, which are detectable in ovarian cancer tumors, suggesting the possibility that epigenetics may also play a key role in the mechanism of long-term effective prevention of ovarian cancer. To our knowledge, there is a lack of high-quality data on the molecular mechanisms of ovarian cancer prevention, although several hypotheses have been proposed.
    CONCLUSIONS: This review focusses on the evidence for a proposed novel hypothesis-that COCPs act as a chemoprevention through the impact on the epigenome of the cells of origin of ovarian cancer-fallopian tubes epithelium.
    Keywords:  COCP; Combined oral contraceptive pill; DNA methylation; Ovarian cancer; Prevention