bims-ovdlit 2021-04-25 papers

Issue of 2021–04–25
five papers selected by
Lara Paracchini, Humanitas Research

Gynecol Oncol. 2021 Apr 20. pii: S0090-8258(21)00330-9. [Epub ahead of print]

Epithelial ovarian cancer and the use of circulating tumor DNA: A systematic review.

Christine Fribert Thusgaard, Malene Korsholm, Kristina Magaard Koldby, Torben A Kruse, Mads Thomassen, Kirsten Marie Jochumsen.

OBJECTIVE: One way to improve the survival rate of epithelial Ovarian Cancer (EOC) is by identifying effective biomarkers useful at different stages and time points of the disease. A potential biomarker is circulating tumor DNA (ctDNA) in plasma or serum. In this systematic review, we provide an overview of applications of ctDNA in EOC to discuss the direction of future research in this field.
METHODS: We performed a systematic search in Pubmed, Embase, and Scopus to identify relevant clinical studies eligible for inclusion. Furthermore, the references in the identified studies and relevant reviews were assessed to identify additional studies. The PRISMA guideline was employed to perform the systematic review, and data from the studies were extracted using piloted data extraction forms.
RESULTS: A total of 36 observational studies were included. The concordance between tumor and ctDNA was assessed in 19 studies, early diagnosis in 1, diagnosis in 23, monitoring of treatment response in 7, detection of reversion mutations in 3, prognosis in 9, but no studies assessed early detection of recurrence. Data from the studies were reported descriptively. The studies had a large variation in the methods used for ctDNA analysis and limited sample sizes of 10-126 patients. Overall, the studies show that ctDNA is a potential biomarker for EOC useful in several settings during assessment and treatment of these patients.
CONCLUSIONS: Although the identified studies are limited in number and their methods for ctDNA analysis vary, it is clear that ctDNA as a biomarker for EOC is promising for several applications in diagnostics, monitoring of treatment response, and prognostics. However, more studies are needed to establish the ideal methods and settings for the clinical use of ctDNA in EOC.

Keywords: Biomarker; Circulating tumor DNA; Epithelial ovarian cancer

DOI: https://doi.org/10.1016/j.ygyno.2021.04.020

Nat Rev Genet. 2021 Apr 19.

Statistical mechanics meets single-cell biology.

Andrew E Teschendorff, Andrew P Feinberg.

Single-cell omics is transforming our understanding of cell biology and disease, yet the systems-level analysis and interpretation of single-cell data faces many challenges. In this Perspective, we describe the impact that fundamental concepts from statistical mechanics, notably entropy, stochastic processes and critical phenomena, are having on single-cell data analysis. We further advocate the need for more bottom-up modelling of single-cell data and to embrace a statistical mechanics analysis paradigm to help attain a deeper understanding of single-cell systems biology.

DOI: https://doi.org/10.1038/s41576-021-00341-z

Cancer Genet. 2021 Apr 05. pii: S2210-7762(21)00099-5. [Epub ahead of print]256-257 31-35

The spectrum of tumors harboring BAP1 gene alterations.

Yael Laitman, Justin Newberg, Rinat Bernstein Molho, Dexter X Jin, Eitan Friedman.

Germline mutations in the BRCA1-associated protein (BAP1) gene (MIM # 603089) are associated with a substantially increased risk for developing melanoma, mesothelioma, and renal cell carcinoma. Somatic inactivation of the BAP1 gene was noted in these and other tumors types, including esophageal cancer and cholangiocarcinoma. The favorable response of BRCA1/2-associated tumors to poly (ADP-ribose) polymerase (PARP) inhibitor therapy, raises the possibility that tumors harboring BAP1 mutations may exhibit similar sensitivity to PARP inhibitor therapy. Given the possibility that BAP1 alterations may have therapeutic implications, this study was aimed to describe the spectrum of tumors that harbor BAP1 alterations. The Foundation Medicine database was queried for known or likely pathogenic BAP1 genomic variants through July 2019. Overall, 4982/374,694 (1.81%) tumors harbored pathogenic BAP1 genomic alterations. Highest rates were noted in mesothelioma (45.24%), cholangiocarcinoma (13.37%), renal cell carcinoma (10.52%), thymic cancer (8.16%), salivary gland cancer (6.18%), and melanoma (5.1%). There were 59 unique BAP1 short variants detected in at least 10 samples. More same tissue tumors of squamous cell histology harbored BAP1 alterations than adenocarcinomas. The current study highlights tumor types that display higher than previously appreciated rates of somatic BAP1 genomic alterations.

Keywords: BAP1 gene; Carcinogenesis; Inactivating genomic alterations; Prognostic implications

DOI: https://doi.org/10.1016/j.cancergen.2021.03.007

Br J Radiol. 2021 Apr 21. 20210002

PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Rowan Miller, Amy Lewis, Melanie E Powell.

Advanced ovarian and endometrial cancers have historically been associated with poor prognosis and few treatment options, limited to single or doublet chemotherapy regimens. The introduction of novel target therapies has transformed the management of these cancers. In contrast to chemotherapy, which inhibits DNA replication and mitosis, targeted therapies target cancer signalling pathways, stroma, immune-microenvironment and vasculature in tumours tissues. The most notable advances in gynaecological cancers have come from the introduction of PARP inhibitors and immune checkpoint inhibitors for ovarian and endometrial cancer respectively. Several PARP inhibitors, which target defective DNA repair have been approved as maintenance therapy for advanced ovarian cancer in both the first line and platinum sensitive relapsed settings. Immune checkpoint inhibitors such as anti PD-1/PD-L1 antibodies have proven successful in advanced mismatch repair deficient endometrial cancers with use now being investigated beyond this population. This review will explore the biological rationale and clinical evidence behind the use of PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

DOI: https://doi.org/10.1259/bjr.20210002