bims-ovdlit 2026-08-23 papers

Issue of 2026–08–23
six papers selected by
Lara Paracchini, Humanitas Research

Genome Res. 2026 Aug 17. pii: gr.281433.125. [Epub ahead of print]

Characterizing intra- and intertumor heterogeneity in ovarian high-grade serous carcinoma subtypes using single-cell and spatial transcriptomics.

Weishan Li, Laurie Grieshober, Jason Gertz, Adriana Ivich, Jennifer A Doherty, Casey S Greene, Stephanie C Hicks.

Ovarian high-grade serous carcinoma (HGSC) is an aggressive ovarian cancer with a heterogeneous tumor microenvironment (TME). Advances in single-cell RNA sequencing (scRNA-seq) and spatially-resolved transcriptomics have enabled the study of complex TME. This study explores connections between molecular subtypes described from bulk transcriptomes and spatial domains characterized by distinct gene expression in HGSC and their variability between patients. We quantify both intra- and intertumor heterogeneity across 2D space and identify differing spatial patterns of gene expression pertaining to immune pathways and vasculature development. Functional characterization of tumor spaces reveals potentially shared cell states across molecular subtypes, while correlation analysis underscores subtype-specific spatial anti-colocalization between spots exhibiting antigen-presenting functions and B cell-mediated immunity. Lastly, we perform spatially-aware cell-cell communication analysis on the spatial samples and identify a molecular subtype specific difference in total signaling activity and heterogeneity in Midkine signaling between the differentiated subtype. Our results suggest that generating multiple tissue slices per patient might be necessary to enable comprehensive characterization of HGSC spatial transcriptomes.

DOI: https://doi.org/10.1101/gr.281433.125

Int J Gynecol Cancer. 2026 Aug 03. pii: S1048-891X(26)00429-9. [Epub ahead of print]36(9): 104898

From genetic testing to prevention: an integrated clinical pathway for hereditary risk assessment in tubo-ovarian cancer.

David Viveros-Carreño, Nathalia Mora-Soto, Isabel Beshar, Nuria Agustí, Lucía Martínez-Cruz, Andreina Fernandes, Alessandro Buda, Alejandro Rauh-Hain, René Pareja.

Hereditary tubo-ovarian cancer risk assessment has evolved from a BRCA1/2-centered consultation to an integrated prevention pathway that begins at diagnosis and extends to unaffected relatives. Germline testing is now justified for patients with epithelial tubo-ovarian cancer because actionable pathogenic variants are common enough that family-history-only referral misses many carriers. The central clinical challenge is no longer whether testing matters, but whether testing is interpreted and implemented in a way that prevents cancer. BRCA1 and BRCA2 remain the highest-impact tubo-ovarian cancer predisposition genes, but Lynch syndrome genes, BRIP1, RAD51C, RAD51D, PALB2, and selected rare histology-directed syndromes require distinct counseling. Gene-specific penetrance, age-specific risk, family history, comorbidities, reproductive plans, and menopause consequences should shape the timing of risk-reducing surgery. Tumor testing improves therapeutic selection and can identify possible hereditary variants, but tumor-only testing does not replace germline testing when hereditary evaluation is indicated. Cascade testing should be measured and resourced as part of tubo-ovarian cancer care rather than treated as a passive family responsibility. Mainstream testing, traceback programs, and navigation-supported cascade testing offer pragmatic implementation models, but access gaps remain. For gynecologic oncology clinicians, modern hereditary risk assessment should be understood as a multi-disciplinary prevention intervention: testing is the entry point, not the endpoint. This narrative review synthesizes gene-specific counseling, tumor-germline interpretation, and implementation strategies into a clinically oriented pathway from diagnosis to prevention for patients and relatives.

Keywords: BRCA1; BRCA2; Cascade Testing; Genetic Testing; Hereditary Cancer; Lynch Syndrome; Ovarian Cancer

DOI: https://doi.org/10.1016/j.ijgc.2026.104898

Oncol Rev. 2026 ;20 1804447

Beyond the hallmarks of cancer: enabling technologies reshaping cancer diagnosis, prevention, and treatment.

Sarfaraz K Niazi.

Cancer biology has been organized for 2 decades by the hallmarks framework, articulated in 2000 and most recently revised in 2026. The pace of technological change in oncology now requires reframing how cancer is detected, prevented, and treated. This review argues that the hallmarks framework, while historically essential, is no longer sufficient on its own to capture contemporary cancer care, and repositions the discussion around enabling technologies that operate across and beyond individual hallmarks. For diagnosis, multi-omic liquid biopsy, AI-assisted radiomics and digital pathology, spatial transcriptomics, single-cell sequencing, and machine-learning analysis of plasma proteomics now support earlier detection, prediction of cancer risk years before diagnosis, monitoring of clonal evolution, and prediction of treatment response. For prevention, the validated population-level success of Human papillomavirus and HBV vaccination is contrasted with investigational directions including mRNA platforms, CRISPR-enabled antigen optimization, personalized neoantigen prophylaxis, and biomarker-stratified molecular interception, none of which has yet been validated in prospective human cancer-prevention trials. For treatment, the discussion is organized by modality class: immune checkpoint inhibitors and resistance strategies, antibody-drug conjugates, bispecific antibodies and T-cell engagers, radioligand therapies, tumor-infiltrating lymphocyte therapy, CRISPR-edited CAR-T and TCR therapies, photonic and photoimmunologic therapies, RNA therapeutics, and adaptive combination regimens. Comparative tables summarize diagnostic platforms, immunotherapeutic modalities, photonic therapies, CRISPR-edited immunotherapy trials, neoantigen vaccine pipelines, and convergent strategies. The trajectory of oncology will be defined less by incremental refinement of hallmarks and more by convergent technologies that integrate diagnostics, prevention, and treatment into continuous, data-driven systems.

Keywords: AI-enabled cancer diagnostics; antibody and radioligand-targeted therapeutics; convergent cancer technologies; immune checkpoint and cellular therapies; mRNA neoantigen vaccines; multi-omic liquid biopsy; photonic and photoimmunologic cancer therapies

DOI: https://doi.org/10.3389/or.2026.1804447

Breast Cancer. 2026 Aug 18.

Hormonal contraceptives and cancer risk in women with a BRCA1 or BRCA2 pathogenic variant.

Chen Nahshon, Leen Fahoum, Dana Hadar, Hila Cohen, Rachel Michaelson-Cohen, Shira Regev, Meirav Schmidt, Wisam Assaf, Steven A Narod, Yakir Segev.

BACKGROUND: Women with BRCA1/2 pathogenic variants face increased risks of breast and ovarian cancers. Our study aimed to evaluate the impact of hormonal contraceptive use on these risks.
METHODS: This matched cohort study included 1677 women who were found to carry a BRCA1/2 pathogenic variant. A Cox proportional hazards model was used to estimate hazard ratios associated with oral contraceptive use and with levonorgestrel-releasing intrauterine device use.
RESULTS: Among BRCA1 carriers (n = 990), oral contraceptive use was not associated with breast cancer risk (HR = 0.90, 95% CI 0.77-1.05, p = 0.2). Among BRCA2 carriers (n = 687), oral contraceptive use was associated with reduced breast cancer risk (HR = 0.80, 95% CI 0.65-0.99, p = 0.04), although duration-stratified analyses did not demonstrate a consistent dose-response relationship. Oral contraceptive use was associated with a decrease in the risk of ovarian cancer in BRCA2 carriers (HR = 0.57, 95% CI 0.35-0.94, p = 0.028), with the strongest protective effect observed among BRCA2 carriers who used an oral contraceptive for more than 5 years (HR = 0.13; 95% CI 0.02-0.92). The protective effect of oral contraceptive use was less profound for BRCA1 carriers. The use of a levonorgestrel-releasing intrauterine device was not associated with breast or ovarian cancer risk.
CONCLUSION: The use of an oral contraceptive was associated with reduced risks of breast and ovarian cancer among BRCA2 carriers, although the observed association with breast cancer should be interpreted cautiously given the absence of a consistent duration-response pattern. There was no increase in the risk of breast cancer among BRCA1 carriers who used an oral contraceptive. No association with either cancer was found among users of a levonorgestrel-releasing intrauterine device.

Keywords: BRCA; Breast cancer; Contraceptives; IUD; Ovarian cancer; Pills

DOI: https://doi.org/10.1007/s12282-026-01890-z

bioRxiv. 2026 Aug 04. pii: 2026.07.27.741055. [Epub ahead of print]

From Wikipedia to AI: Measuring 25 years of synthesis of human genetics research in the public-facing information ecosystem.

Alex Diaz-Papkovich, Abigail Kuntzleman, Sophia C Davis, Sohini Ramachandran.

Genetics research frequently intersects with ethnicity, nationality, and race, making it uniquely vulnerable to misrepresentation. Yet, 25 years after the initial sequencing of the human genome, there is little understanding of how human genetics research exists in the public-facing information ecosystem. We analyze 3,050,422 historical revisions from 6,738 Wikipedia pages about ethnicity, nationality, and race spanning 25 years. We find genetics terminology is present in 14.8% of these pages (55.5% in the top 1,000 pages) and in 67.8% of pages about nationalities, suggesting research is synthesized to present a biological element to ethnicity and nationality. We also find that 10.1% of 56,908 discussions from these pages contain genetics terminology. We further analyze responses from three popular chatbots queried about nationalities and find that they commonly reference both genetics and Wikipedia. Lastly, we analyze 133 pages from Grokipedia, an AI-generated encyclopedia, and find it mentions genetics more frequently than Wikipedia and hallucinates or misrepresents human genetics research.

DOI: https://doi.org/10.64898/2026.07.27.741055