bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–03–08
twelve papers selected by
Lara Paracchini, Humanitas Research
  1. Cell-free DNA fragmentomes for noninvasive detection of liver cirrhosis and other diseases.
  2. Ovarian cancer.
  3. Ovarian cancer.
  4. Risk of Breast Cancer After Ovarian Cancer in Women With a Pathogenic/Likely Pathogenic Variant in BRCA1 or BRCA2.
  5. From Serum Markers to Liquid Biopsy: Precision Monitoring in Breast, Ovarian, Pancreatic, and Prostate Cancers.
  6. Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma.
  7. Risks of non-breast, non-ovarian cancers for BRCA1 and BRCA2 pathogenic variant carriers: a prospective cohort study.
  8. Harnessing genomics for early cancer detection, risk stratification and prevention.
  9. The impact of the patient macroenvironment on molecular subgroups in endometrial cancer.
  10. De-escalation in stage IC epithelial ovarian cancer: adjuvant treatment.
  11. Homologous recombination deficiency and hemizygosity drive resistance in breast cancer.
  12. Familial colorectal cancer: risk factors, screening strategies and personalized medicine.
  1. Sci Transl Med. 2026 Mar 04. 18(839): eadw2603
    Cell-free DNA fragmentomes for noninvasive detection of liver cirrhosis and other diseases.
    Akshaya V Annapragada, Zachariah H Foda, Hope Orjuela, Carter Norton, Shashikant Koul, Noushin Niknafs, Sarah Short, Keerti Boyapati, Adrianna Bartolomucci, Dimitrios Mathios, Michael Noë, Chris Cherry, Jacob Carey, Alessandro Leal, Bryan Chesnick, Nicholas C Dracopoli, Jamie E Medina, Nicholas A Vulpescu, Daniel C Bruhm, Sarah Bacus, Vilmos Adleff, Amy K Kim, Stephen B Baylin, Gregory D Kirk, Andrei Sorop, Razvan Iacob, Speranta Iacob, Liana Gheorghe, Simona Dima, Manuel Ramírez-Zea, Katherine A McGlynn, Claus L Feltoft, Julia S Johansen, John Groopman, Jillian Phallen, Robert B Scharpf, Victor E Velculescu.
      Accessible liquid biopsies, including analyses of genome-wide cell-free DNA (cfDNA) fragmentation, are emerging for early detection of cancer but remain largely unexplored in other diseases. Here, we used whole-genome sequencing to examine cfDNA fragmentomes in 1576 individuals, including those with liver disease or with other morbidities such as vascular, autoimmune, and neurodegenerative conditions. As a prototype for disease-specific cfDNA fragmentomic biomarkers, we developed a machine learning classifier that detected early liver disease, advanced fibrosis, and cirrhosis with high sensitivity in separate discovery (n = 423) and validation cohorts (n = 221) and had limited cross-reactivity for other diseases. Genome-wide fragmentome and methylome analyses revealed liver-derived and immune-mediated changes in cfDNA in the circulation of individuals affected with liver disease. Fragmentomic changes were also observed across a range of other human morbidities and reflected disease-specific changes in the circulation. A machine learning model using cfDNA fragmentomes predicted overall survival in separate morbidity discovery (n = 571) and validation cohorts (n = 231). These analyses demonstrate the connection between cfDNA fragmentomes and an individual's physiologic state and provide previously unrecognized possibilities for cfDNA liquid biopsies across human disease.
    DOI:  https://doi.org/10.1126/scitranslmed.adw2603
  2. Nat Rev Dis Primers. 2026 Mar 05. pii: 9. [Epub ahead of print]12(1):
    Ovarian cancer.
      
    DOI:  https://doi.org/10.1038/s41572-026-00690-1
  3. Nat Rev Dis Primers. 2026 Mar 05. pii: 10. [Epub ahead of print]12(1):
    Ovarian cancer.
    Clare L Scott, Susana Banerjee, Florence Joly, Jung-Min Lee, Asima Mukhopadhyay, David S Tan, Elise C Kohn.
      Epithelial ovarian cancer (EOC) describes a group of diseases characterized by differing pathogeneses, molecular profiles, histologies and prognoses. The low incidence of each distinct histological type of EOC poses challenges for obtaining an accurate diagnosis, robust evidence to guide management, and a mechanistic understanding to ensure availability of effective therapies. Most EOCs, including high-grade serous ovarian cancer, predominantly originate from the fimbriated ends of the fallopian tube, whereas low-grade serous, clear cell, endometrioid and mucinous EOCs are thought to originate from other tissues. Despite recognized genetic susceptibilities for the disease, no effective screening is available and late-stage diagnosis remains common. Known genetic susceptibilities are addressed by risk reduction surgery including removal of both fallopian tubes and both ovaries. Management is predominantly based on adequate surgery and chemotherapy with carboplatin and paclitaxel, with the addition of anti-angiogenic therapy as indicated. The incorporation of poly(ADP-ribose) polymerase inhibitors into first-line therapy has considerably altered outcomes in some women with EOC who have defective homologous recombination DNA repair, including in those with BRCA1 and/or BRCA2 mutations. Other molecular characteristics are important in distinct types of EOC, but the use of matched targeted therapies remains under investigation, as does the role of immunotherapy for EOC, for which trial data have been disappointing to date. Translationally enriched clinical trials will be important to further explore and validate accurate biomarkers to better guide clinical care.
    DOI:  https://doi.org/10.1038/s41572-026-00686-x
  4. J Clin Oncol. 2026 Feb 28. JCO2501648
    Risk of Breast Cancer After Ovarian Cancer in Women With a Pathogenic/Likely Pathogenic Variant in BRCA1 or BRCA2.
    Hereditary Breast Cancer Clinical Study Group
       PURPOSE: BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer.
    METHODS: We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2, a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer.
    RESULTS: A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer-related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001).
    CONCLUSION: After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.
    DOI:  https://doi.org/10.1200/JCO-25-01648
  5. Semin Oncol Nurs. 2026 Mar 05. pii: S0749-2081(26)00047-1. [Epub ahead of print] 152167
    From Serum Markers to Liquid Biopsy: Precision Monitoring in Breast, Ovarian, Pancreatic, and Prostate Cancers.
    Laurie M Connors, Carmen S Rodriguez, Christopher Tan, Fadi Gouda, Dorothie Durosier Mertilus.
       OBJECTIVES: This article is a detailed exploration of the clinical utility, strengths, and limitations of traditional serum tumor markers with emerging circulating cell-free DNA (cfDNA) technologies in the monitoring of breast, ovarian, pancreas, and prostate cancers. It highlights how integrated biomarker strategies can advance precision oncology, particularly in the context of hereditary breast, ovarian, pancreas, and prostate cancer syndrome.
    METHODS: A review was conducted of current literature and practice guidelines, including the latest updates from the National Comprehensive Cancer Network (NCCN). The clinical performance, diagnostic value, and monitoring roles of serum tumor markers (eg, CA 15-3, CA 125, PSA, CA 19-9) and cfDNA were discussed descriptively across these four malignancies. Emphasis was placed on evidence relevant to hereditary cancer risk assessment, therapeutic decision-making, and disease surveillance.
    RESULTS: Serum tumor markers remain a cornerstone in oncology nursing practice because of the accessibility and utility in assessing treatment response and tracking disease burden over time. Yet, their limited sensitivity and specificity, especially for early detection, underscore the need for complementary tools. Circulating cell-free DNA (cfDNA) technologies provide real-time molecular information on tumor biology, offering earlier detection of recurrence, identification of germline-related actionable mutations, and dynamic assessment of therapeutic resistance. In hereditary cancer syndromes such as those associated with BRCA1/2, cfDNA has shown value for detecting minimal residual disease, informing targeted therapy selection (eg, PARP inhibitors), and supporting noninvasive longitudinal monitoring across the cancer care continuum.
    CONCLUSIONS: Integrating cfDNA analysis with traditional serum tumor marker monitoring strengthens the ability to perform comprehensive risk assessment, tailor treatment decisions, and refine disease surveillance for individuals with hereditary cancer risk. This combined approach enables person-centered, evidence-based care while educating patients about the purpose and limits of each test, coordinating timely follow-up, and supporting adherence to surveillance protocols thereby ultimately improving outcomes for high-risk populations.
    IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses play a critical role in supporting the integration of advanced biomarker technologies into personalized care. Understanding the evolving applications of cfDNA and serum tumor markers is essential for patient education, shared decision-making, and advocacy for equitable access to precision oncology innovations. Nurses are key partners in implementing biomarker-informed care pathways that promote individualized, high-quality cancer care.
    Keywords:  BRCA; Biomarkers; Oncology; Precision; Surveillance; cfDNA
    DOI:  https://doi.org/10.1016/j.soncn.2026.152167
  6. EMBO Mol Med. 2026 Mar 06.
    Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma.
    Sophie A Richardson, Aram Safrastyan, Mina Karimpour, Gayatri Gulati, Patrick J B Harker, Alan Redfern, Simon P Pearce, Vsevolod J Makeev, Bernadette Brennan, Alexander T J Lee, Alexandra Clipson, Steven M Hill, Caroline Dive, Dominic G Rothwell, Martin G McCabe, Florent Mouliere.
      Liquid biopsies and cell-free DNA (cfDNA) offer minimally invasive methods for the diagnosis and monitoring of Ewing Sarcoma (EwS). EwS have a low tumour mutational burden and their detection with plasma cfDNA is challenging. We hypothesised that analysing the cfDNA methylome and fragmentome could enhance sensitivity for detecting EwS and identifying disease recurrence. Using T7-MBD-seq, we conducted whole-genome and methylome sequencing of cfDNA from 87 serial samples of 23 patients with EwS and 3 patients with CIC-rearranged sarcoma (CIC). With EwingSign, a new machine learning model, we identified EwS or CIC in a test set for 11 out of 16 patients at diagnosis and 15 out of 18 clinically confirmed relapse events. 0 out of 24 non-cancer controls (NCC) were detected positive with EwingSign. When combined with global and regional fragmentome analysis, all 18 relapse cases were detected, with 15/18 detected by 2 or more modalities, and 1 out of 24 NCC was detected by one modality. These findings indicate that cfDNA methylome and fragmentome analysis, if validated in a larger cohort, could improve disease detection, monitoring and relapse identification in patients with EwS.
    Keywords:  Cell-Free DNA; Ewing Sarcoma; Fragmentomics; Liquid Biopsy; Methylome
    DOI:  https://doi.org/10.1038/s44321-026-00396-7
  7. BMC Med. 2026 Mar 04.
    Risks of non-breast, non-ovarian cancers for BRCA1 and BRCA2 pathogenic variant carriers: a prospective cohort study.
    Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer (kConFab)
       BACKGROUND: The non-breast non-ovarian cancers associated with BRCA1 and BRCA2 pathogenic variants (PVs) are controversial. We aimed to examine this using a prospective cohort design.
    METHODS: This study included 1260 BRCA1 and 1058 BRCA2 PV carriers (91% were females) from two consortia: the Breast Cancer Family Registry (BCFR) and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Follow-Up Study (kConFab-FUS). The carriers were free of cancer other than breast or ovarian cancer at baseline and had a median baseline age of 45.5 years. For 16 types of non-breast, non-ovarian cancers, standardized incidence ratios (SIRs) relative to population incidence, the probabilities of relative risk effect size > 2 (i.e., moderate risk) and cumulative risks to age 80 years were estimated.
    RESULTS: During a median follow-up time of 11.4 years, 161 non-breast, non-ovarian cancers were observed. For BRCA1 PV carriers, little evidence of increased risk was observed. The prostate, pancreatic, and all non-pancreatic cancer SIRs were 1.7 (95% CI 0.7-4.2), 1.1 (95% CI 0.3-4.6) and 0.85 (95% CI 0.68-1.06), respectively; the probabilities of relative risk > 2 were 0 and 67% for prostate and pancreatic cancers, respectively. For BRCA2 PV carriers, increased risks of pancreatic (SIR = 6.6, 95% CI 3.8-11.6), prostate (SIR = 3.6, 95% CI 1.9-6.8) and stomach (SIR = 3.1, 95% CI 1.01-9.8) cancer were observed, with a cumulative risk to age 80 years of 8.3, 82.0, and 1.6%, respectively. For all the other non-breast, non-ovarian cancers combined, the SIR was 0.85 (95% CI 0.66-1.10).
    CONCLUSIONS: Apart from pancreatic, prostate, and possibly stomach cancers for BRCA2 PV carriers, and possibly pancreatic cancer for BRCA1 PV carriers, there is no evidence that BRCA1 and BRCA2 PV carriers have substantially increased risks of other non-breast, non-ovarian cancers. Our prospective risk estimates are informative for cancer risk assessment for people with BRCA1 and BRCA2 PVs.
    Keywords:   BRCA1 ; BRCA2 ; Cancer risk; Penetrance; Prospective study
    DOI:  https://doi.org/10.1186/s12916-026-04753-8
  8. Nat Genet. 2026 Mar 02.
    Harnessing genomics for early cancer detection, risk stratification and prevention.
    Muxin Gu, Woody Z Zhang, Rebecca C Fitzgerald, Alexander M Frankell, George S Vassiliou.
      Therapeutic advances have improved cancer outcomes, but early-stage detection remains the single most important determinant of favorable prognoses across many cancer types. Cancer genomics has yielded detailed maps of somatic mutation and methylation patterns characteristic of different cancers, enabling the development of assays to detect mutation-bearing tumor-derived DNA in tissue biopsies, blood and other body fluids at the earliest stages of disease. In parallel, it has also become clear that small clones bearing cancer-associated mutations arise commonly in histologically normal tissues, a phenomenon that becomes universal in proliferative tissues with age but leads to cancer in only a small minority of individuals. This review article outlines established strategies for early cancer detection and highlights emerging insights into the genetics of precancerous mutant clones that have led to the recent development of prognostic frameworks for identifying high-risk individuals, making it increasingly possible to intercept evolving cancer at a premalignant or early malignant stage, when interventions are most effective.
    DOI:  https://doi.org/10.1038/s41588-026-02505-1
  9. Cancer. 2026 Mar 15. 132(6): e70333
    The impact of the patient macroenvironment on molecular subgroups in endometrial cancer.
    ENITEC Consortium
      More than half of endometrial cancer diagnoses can be attributed to obesity. A purely molecular classification in endometrial cancer hampers further understanding of the impact of patient macroenvironment as a major risk factor. The relationship between patient factors, such as age, body mass index (BMI), comorbidity, and ethnicity, and molecular subgroups was studied in a publicly available data set (N = 225) and two multicenter European cohorts (N = 223; N = 946). Age at diagnosis was highest in the TP53-mutated subgroup, and differed significantly between molecular subgroups. Patients with obesity were younger at diagnosis compared to their lean counterparts across all molecular subgroups (61.9 vs. 66.2 years; p < .01). Survival was worst in the TP53-mutated subgroup but improved with increasing BMI, which resulted in nonsignificant differences from other subgroups when BMI was >35. These data underscore that patient factors remain important, and their integration with molecular factors needs to be better understood to ultimately improve treatment and prevention strategies in endometrial cancer.
    Keywords:  body mass index; comorbidity; endometrial neoplasm classification; ethnicity; health behavior; obesity; prognosis; risk factors
    DOI:  https://doi.org/10.1002/cncr.70333
  10. Int J Gynecol Cancer. 2026 Mar 02. pii: S1048-891X(25)01940-1. [Epub ahead of print] 102818
    De-escalation in stage IC epithelial ovarian cancer: adjuvant treatment.
    Christian Dagher, Minyoung Jang, Dimitrios Nasioudis.
      Epithelial ovarian cancer is a heterogenous group, that includes histologic sub-types with distinct biologic behavior. Stage IC disease confers a higher risk of recurrence and death compared to stage IA. While adjuvant chemotherapy may improve outcomes of patients with high-grade serous ovarian carcinoma, its impact on the oncologic outcomes of other histologic sub-types that are more chemo-resistant, such as clear cell, mucinous, and low-grade serous ovarian carcinoma is not well-established. Retrospective studies have demonstrated that omission of adjuvant chemotherapy can be considered for patients with expansile mucinous, grade 1 endometrioid, and low-grade serous ovarian carcinoma and for those with stage IC1 clear cell ovarian carcinoma. However, in the absence of data from randomized clinical trials, shared decision-making, and careful counseling of patients should be considered. Future multicenter studies are required to further validate the safety of adjuvant chemotherapy omission in certain patient sub-groups with stage IC epithelial ovarian cancer.
    Keywords:  Chemotherapy; Early Stage; Ovarian Cancer
    DOI:  https://doi.org/10.1016/j.ijgc.2025.102818
  11. Nature. 2026 Mar 04.
    Homologous recombination deficiency and hemizygosity drive resistance in breast cancer.
    Anton Safonov, Minna Lee, David N Brown, Luca Boscolo Bielo, Miika Mehine, Chaitanya Bandlamudi, Ben O'Leary, Hong Shao, Laia Vicente, Daniel Muldoon, Allen Zhu, Susana Ros, Antonio Marra, Pier Selenica, Ivan Bieche, Bradley Wubbenhorst, Emanuela Ferraro, Laura Courtois, Rania El Botty, Mehnaj Ahmed, Enrico Moiso, Julia Ah-Reum An, Mark T A Donoghue, Marie Will, Fresia Pareja, Emily Nizialek, Natalia Lukashchuk, Eleni Sofianopoulou, Yuan Liu, Xin Huang, Colombe Chappey, Anna D Staniszewska, Dara Ross, Diana Mandelker, Marc Ladanyi, Nikolaus Schultz, Michael F Berger, Maurizio Scaltriti, Jorge S Reis-Filho, Bob T Li, Kenneth Offit, Larry Norton, Ronglai Shen, Kara N Maxwell, Fergus Couch, Susan M Domchek, Elisabetta Marangoni, Sohrab Shah, Mark R Albertella, Violeta Serra, Britta Weigelt, David B Solit, Katherine L Nathanson, Mark E Robson, Nicholas C Turner, Sarat Chandarlapaty, Pedram Razavi.
      The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, yet their combined influence on tumour evolution and therapy resistance remains poorly defined. Through an integrated clinicogenomic analysis of more than 5,800 patients, we show that germline (g) pathogenic variants dictate the evolutionary trajectory of acquired resistance. We specifically find that gBRCA2-associated tumours are uniquely predisposed to develop acquired RB1 loss-of-function alterations, resulting in poor outcomes on standard-of-care frontline CDK4/6 inhibitor (CDK4/6i) combinations. This vulnerability is driven by a dual mechanism: baseline RB1 hemizygosity (heterozygous loss resulting in a single functional RB1 allele), which lowers the evolutionary barrier to biallelic inactivation, and ongoing homologous recombination deficiency, which promotes acquisition of RB1 loss-of-function alterations under the selective pressure of CDK4/6i. Preclinical models from gBRCA2 carriers showed near-uniform resistance to CDK4/6i, with consistent post-treatment Rb loss. Across multiple independent models and in our clinical data, PARP inhibition consistently outperformed CDK4/6i. Our findings suggest that prioritizing PARP inhibition in gBRCA2 carriers may intercept RB1-loss trajectories and delay resistance. More broadly, we establish a predictive framework for forecasting drug-resistant trajectories based on pre-treatment allelic configuration and mutational signatures.
    DOI:  https://doi.org/10.1038/s41586-026-10197-0
  12. Cancer Genet. 2026 Feb 23. pii: S2210-7762(26)00028-1. [Epub ahead of print]302-303 166-175
    Familial colorectal cancer: risk factors, screening strategies and personalized medicine.
    Pungă Maria-Alexia, Radu Cristina, Treteanu Andreea-Ramona, Andronic Octavian, Rădoi Viorica.
      Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with approximately 25-30 % of cases exhibiting a familial component driven by germline mutations in DNA mismatch repair genes (Lynch syndrome) or the APC gene (familial adenomatous polyposis). Despite advances in screening and early detection, significant challenges persist in identifying at-risk individuals, optimizing surveillance strategies and addressing disparities in access to genetic testing and preventive care. This narrative review synthesizes current evidence on the genetic underpinnings, modifiable risk factors and personalized screening approaches for familial CRC. We highlight the critical interplay between hereditary predisposition and environmental exposures including diet, obesity, smoking and gut microbiome alterations, which cumulatively influence disease penetrance and clinical outcomes. Emerging predictive models integrating family history, polygenic risk scores and proteomic biomarkers offer unprecedented opportunities for risk stratification, enabling tailored screening initiation and intervals that balance clinical efficacy with cost-effectiveness. Novel non-invasive biomarkers, such as circulating tumor DNA and stool RNA tests, demonstrate promising sensitivity and specificity, potentially enhancing patient adherence while complementing gold-standard colonoscopy. Furthermore, artificial intelligence-assisted endoscopy and comprehensive genetic panels are reshaping precision oncology by improving adenoma detection rates and guiding targeted therapies. Addressing social determinants of health and implementing structured genetic counseling remain essential to achieving equitable CRC prevention. By transitioning from age-based to individualized, risk-adapted screening paradigms, healthcare systems can significantly reduce CRC incidence and mortality, particularly among genetically predisposed populations.
    Keywords:  Familial colorectal cancer; Genetic risk; Hereditary cancer syndroms; Lynch syndrome; Personalized medicine; Screening strategies
    DOI:  https://doi.org/10.1016/j.cancergen.2026.02.008
This page is being maintained by Thomas Krichel. It was last updated on 2026‒03‒24 at 10:49.