Introduction:Multimodal large language models (LLMs) can process text and images to support diagnostic processes, yet their ability to apply standardized ovarian ultrasound classification systems remains unexplored. This study evaluates Google Gemini's performance with regard to interpreting ovarian ultrasound using the Ovarian-Adnexal Reporting and Data System (O-RADS) and International Ovarian Tumor Analysis (IOTA) criteria (IOTA simple rules) compared to expert evaluation. Methods:This retrospective study included 30 ultrasound examinations from the University Hospital of Basel: 10 normal ovaries, 10 benign lesions, and 10 malignant lesions. Each examination included B-mode and Doppler images. Google Gemini was prompted to assess normal ovarian images for pathology and apply the O-RADS categories and IOTA simple rules to pathologic cases. Two blinded experts independently evaluated responses using the Global Quality Score (GQS, 1-5 scale). The reference standard was histopathology for pathologic cases and expert assessment for normal ovaries. Results:Google Gemini achieved a mean GQS of 3 across all categories. The model mischaracterized 6/10 normal ovaries as pathologic. For benign lesions, 6/10 were incorrectly assigned to high-risk O-RADS categories (4-5) with frequent misidentification of malignant IOTA features. While 6/10 malignant cases were correctly identified (GQS 4-5), 3/10 were misclassified as benign (O-RADS 2, GQS 1). The remaining case of a mucinous borderline tumor was also misclassified by the LLM (O-RADS 3, GQS 1). Conclusion:Google Gemini seems to not be ready for independent clinical application in ovarian ultrasound interpretation. Critical inconsistencies including overdiagnosis and dangerous misclassification of malignancies indicate the need for specialized, domain-specific models with rigorous validation before clinical implementation.
BACKGROUND/OBJECTIVES:Ovarian cancer is typically diagnosed in postmenopausal women, so there are limited data available for young adult cancer survivors (YACS). The aim was to assess the patient perspective of YACS. METHODS:In this international and multicenter cross-sectional survey study, patient history, long-term side effects, and patient perspective were assessed. Long-term survival was defined as survival of at least five years after cancer diagnosis. Two groups were defined: (1) 18-40 years and (2) ≥41 years. RESULTS:Altogether, 1833 long-term survivors (LTS) have been recruited, with 1771 patients ≥41 years and 62 patients 18-40 years at recruitment. FIGO stages were similar; among the patients, 99.0% had received primary surgery followed by chemotherapy in 90.3%. Almost 50% still experienced long-term side effects. Patients ≤ 40 years reported more frequently not only gastrointestinal symptoms such as nausea/vomiting (44.4%, p = 0.01), bloating (59.3%, p = 0.038), and constipation (60%, p = 0.015) but also depression (31.4%, p = 0.02), lymphedema (45.3%, p = 0.026), and concentration difficulties (30.6%, p = 0.002). Distress levels were also higher in YACS, especially concerning insurance/finances, work/school, child care, worries, and sadness. Polyneuropathy and secondary cancer were the only side effects that were more frequent in the elder cohort (polyneuropathy: 20.3% vs. 4.3%, p = 0.002, and secondary cancer: 8.4% vs. 0%, p = 0.014). YACS were more physically active (p = 0.003) and interested in studies about long-term cancer survivorship in 87.2%. CONCLUSIONS:Long-term side effects are equally common in YACS after ovarian cancer, but with a focus on practical problems, mental health, gastrointestinal problems, and sexuality. This knowledge should be incorporated into follow-up care of ovarian cancer patients in order to improve quality of life.
BACKGROUND:Immune checkpoint inhibitors have revolutionized cancer therapy, yet a substantial proportion of patients exhibit primary or acquired resistance. Immunocytokines offer a strategy to enhance antitumor immunity by delivering cytokine signals selectively to the tumor microenvironment. Here, we describe the immunoconjugate anti-programmed cell death protein 1 (PD-1)-interleukin (IL)-18 (aPD1-IL18mut), designed to couple PD-1-blockade with localized IL-18-mediated immune activation. METHODS:aPD1-IL18mut was generated by chemically conjugating the anti-human PD-1 antibody Lipustobart to an IL-18 variant engineered to evade IL-18 binding protein. Its mechanism of action was characterized using human PD-1 transgenic mouse models. To assess the translational relevance of these in vivo findings, complementary in vitro assays were conducted on human tumor samples, alongside analyses of publicly available single-cell RNA sequencing datasets. RESULTS:In vitro, PD-1 engagement enhanced functional IL-18 activity, preserving interferon (IFN)-γ secretion even under IL-18BP pressure. In MC38 tumors, aPD1-IL18mut induced robust CD8+ T cell-driven tumor control, accompanied by intratumoral accumulation of activated CD8+ T cells and a pronounced type 1-associated cytokine response. In anti-PD-1-resistant YUMM1.7 tumors, therapeutic efficacy instead relied predominantly on Th1-like CD4+ effector T cells, and aPD1-IL18mut stimulation was associated with enhanced activation, proliferation, IFN-γ, and granzyme B expression in PD-1+IL-18Rɑ+ CD4+ T cells. In human cancer digest cultures, aPD1-IL18mut elicited a dominant IL-18/IFN-γ-driven cytokine signature and enhanced tumor cell killing. Importantly, analyses of the immune infiltrate across multiple human solid tumor types identified analogous PD-1+IL-18Rɑ+ CD4+ Th1-like and CD8+ effector-like T-cell subsets with effector-associated and tumor-reactive transcriptional and protein signatures. CONCLUSIONS:aPD1-IL18mut activates T-cell populations with tumor-reactive features and promotes IFN-γ-driven inflammation across distinct tumor immune contexts. Its ability to activate CD8+ and CD4+ Th1-like effector cells, together with the presence of analogous subsets in multiple human cancers, provides mechanistic and translational support for PD-1-targeted IL-18 therapy.
OBJECTIVE:To evaluate longitudinal trends in gender and regional equity in membership and governance representation within the European Society of Gynaecological Oncology and the European Network of Young Gynaecological Oncologists. METHODS:We analyzed European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership and governance data from 2013 to 2024. Descriptive analyses were supplemented with multi-variable logistic regression models to identify predictors of female membership and European Society of Gynaecological Oncology Council representation, including European Network of Young Gynaecological Oncologists status, calendar year or Council term, and United Nations geographic region. RESULTS:European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership increased from 1588 members in 2013 to 3385 in 2024, and female members reached parity by 2024. Female membership was associated with European Network of Young Gynaecological Oncologists participation (odds ratio 1.82, 95% confidence interval 1.73 to 1.91, p <.001) and calendar year (odds ratio 1.04 per year, 95% confidence interval 1.03 to 1.05, p <.001). Compared with Western Europe, female membership was higher in Northern Europe (odds ratio 1.69, 95% confidence interval 1.55 to 1.84, p <.001) and lower in Eastern Europe (odds ratio 0.78, 95% confidence interval 0.71 to 0.85, p <.001) and non-European regions (odds ratio 0.80, 95% confidence interval 0.74 to 0.86, p <.001). Gender was not associated with Council membership (odds ratio 0.95, 95% confidence interval 0.63 to 1.42, p =.79), and no independent temporal trend was observed (odds ratio 0.91 per term, 95% confidence interval 0.81 to 1.03, p =.13). Geographic variation was evident, with lower odds of Council representation in Eastern Europe (odds ratio 0.54, 95% confidence interval 0.28 to 0.98, p =.05), while estimates for non-European regions were unstable because of sparse representation. CONCLUSIONS:European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists have made substantial progress toward gender equity at the membership level, largely through early-career engagement. Governance representation appears to be influenced more by geographic and structural factors than by gender, highlighting the need for equity-focused strategies that sustain gender-balanced leadership development while addressing regional disparities.
Background/Objectives: Sister Mary Joseph's nodule (SMJN) is classified as FIGO stage IVb in ovarian cancer. While traditionally considered an indicator of poor prognosis, emerging evidence suggests variable outcomes. This study aimed to describe overall survival (OS) and recurrence-free survival (RFS) in ovarian cancer patients presenting with SMJN and to explore outcome patterns relative to other FIGO IVb presentations. Methods: We conducted a retrospective multicenter cohort study including patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma diagnosed between 2010 and 2023 at four academic centers in Switzerland, Italy, and Israel. Eligible patients had FIGO IV disease at diagnosis and complete clinical data. Patients were grouped according to metastatic pattern: SMJN or other distant sites. Survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards models. Results: Eighty-seven patients met inclusion criteria, including 23 (26.4%) with SMJN and 64 (73.6%) with other FIGO IV metastases. Median age and histologic subtype distribution were similar between groups. Complete cytoreduction was achieved in 65.2% of SMJN patients. Median OS was not reached in the SMJN group versus 47.2 months in controls (HR 0.44; 95% CI 0.17-1.12; p = 0.084). Median RFS was 42.6 vs. 23.2 months, respectively (HR 0.68; 95% CI 0.35-1.32; p = 0.25). Conclusions: Patients presenting with SMJN may represent a potentially resectable manifestation within the heterogeneous spectrum of FIGO stage IV ovarian cancer, with a non-significant trend toward more favorable survival outcomes compared with other stage IV presentations.
Abstract In women with high-grade serous ovarian cancer, chemotherapy remains the primary standard treatment, despite growing recognition of the disease as highly heterogeneous. Here, we examine the feasibility and clinical utility of comprehensive multimodal molecular profiling to inform treatment decisions. We analyze blood, single-cell and bulk tumor tissue, and malignant ascites using up to eleven technologies (DNA, RNA, protein, and functional assays) within a four-week turnaround time. Hypothetical treatment recommendations are altered for 76% of patients, and multi-omics-guided maintenance therapy is associated with prolonged overall survival in a subset of patients. Subsequent cohort analysis reveals distinct cellular and molecular profiles in ascites-derived single-cells compared to solid tumor tissue, unique per-patient ex vivo drug responses, and a marked increase in cancer cell heterogeneity following chemotherapy exposure. This coincides with genomic signature alterations in whole-genome-amplified patients. Our data suggest that molecularly guided treatments should be tested as adjuvant therapies prior to chemotherapy in the future.
Effective management of advanced epithelial ovarian cancer (EOC) is challenging, with most patients relapsing despite standard therapies, highlighting the need for personalized treatment. Functional ex vivo drug testing enables matching patients to effective therapies based on drug sensitivity. We present DRUGSENS, a scalable, clinically adaptable ex vivo screening platform that quantitatively assesses single-cell, on-target drug effects in cell lines and patient-derived samples. DRUGSENS offers high-resolution analysis of responses to single agents and relevant drug combinations, guiding personalized treatment across tumor types. The semi-automated assay integrates immunofluorescence-based confocal imaging with computational analysis using QuPath, Fiji, and a dedicated R package. We profiled 21 samples from 17 patients in chemotherapy-naive and relapsed states, achieving 100% culture success and delivering results within 10 days. Most samples showed limited sensitivity to multiple agents, indicating multidrug resistance. Notably, ex vivo drug responses correlated significantly with progression-free and overall survival. DRUGSENS supports rapid, clinically relevant functional profiling in EOC, providing a valuable tool to inform treatment recommendations and prioritize drugs for clinical application.
High-grade serous ovarian carcinoma (HGSC) is the most common epithelial ovarian cancer subtype, with high recurrence rates and poor overall survival. Despite progress with cytoreductive surgery, platinum-based chemotherapy, and poly(ADP-ribose) polymerase (PARP) inhibitors, treatment outcomes remain poor, underscoring the need for novel approaches. Immunotherapy is currently the standard of care for the management of several solid tumors, but its role in HGSC is still emerging.This review synthesizes current evidence on the immune landscape of HGSC, predictive biomarkers, resistance mechanisms, and therapeutic strategies including immune checkpoint inhibitors, vaccines, adoptive cell therapies, oncolytic viruses, and antibody-drug conjugates (ADCs) which interact with the immune system. While checkpoint blockade has demonstrated modest efficacy in unselected populations, ADCs targeting folate receptor alpha (FRα) and trophoblast cell-surface antigen 2 (TROP2) have shown the most encouraging clinical results. Biomarkers such as homologous recombination deficiency, programmed cell death protein ligand 1 (PD-L1) expression, tumor mutational burden, and neoantigen load may enable patient selection, although none are fully validated for immunotherapies. Combination regimens with PARP inhibitors, anti-angiogenic agents, or chemotherapy offer potential synergy, but optimal sequencing remains undefined.Toxicity management is essential, as immune-related adverse events, although generally manageable, may overlap with the side effects of other systemic therapies. Multidisciplinary approaches and patient education are key to safe integration.Overall, immunotherapy represents a promising avenue for selected patients with HGSC. ADCs are leading current clinical advances. Future priorities include biomarker-driven trial designs, strategic treatment sequencing, and innovative combination strategies to maximize therapeutic benefit while minimizing toxicity.
Background: Long-term survivors (LTS) after gynecological cancer may be cured but still face physical and psychological challenges. This multicenter study aimed to assess the long-term side effects, the received follow-up care, and the personal perspectives of survivors. Methods: Between 2019 and 2025, LTS from four European countries within the ENGOT (European Network of Gynecological Oncological Trial Groups) and GCIG (Gynecologic Cancer InterGroup) networks were recruited. Long-term survival was defined as surviving at least five years after the first diagnosis. LTS completed a questionnaire with 81 questions (patient's characteristics, oncological history, current health status, lifestyle factors). Analyses were mainly descriptive. Results: A total of 677 LTS were enrolled, with a median age of 64.0 years (range: 26-92) and a median survival time of 7 years (range: 5-38). A total of 46.6% were diagnosed with cervical cancer, 32.9% with endometrial cancer, 4.4% with ovarian cancer, and 16.1% with other types of gynecological cancer. Moreover, 36.9% still suffer from physical and psychological symptoms, most frequently being lymphedema (36.2%), hot flashes (22.4%), difficulties with concentration (21.1%), fatigue (20.9%), vaginal dryness (20.1%), and urinary incontinence (18.9%). Median overall health status was ranked (scale 1-5; 1 = very good, 5 = very poor) as 2, while 13.5% rated their health as poor/very poor. Current symptoms were associated with poorer health status (p < 0.001) and a history of recurrent disease (p = 0.001). In addition, 13.6% reported not receiving follow-up care. CA-125 was determined in 80.8% of ovarian LTS, as well as in 30.7% of cervical and 28.9% of endometrial LTS. Pap smear follow-up was reported by 50.5% of endometrial LTS. A total of 33.7% did not exercise at all or exercised less than an hour per week, 13.4% smoke tobacco, and 51.2% drink alcohol more often than once a month. Conclusions: Our findings highlight the need for patient-centered follow-up care, addressing both long-term side effects and education on lifestyle and prevention. Follow-up procedures that do not follow guidelines should be avoided.
Purpose: The relationship between the number of initial metastases and metastatic spread in terms of progression-free survival (PFS) and overall survival (OS) in metastatic breast cancer (mBC) remains poorly understood. This study aimed to identify key factors influencing disease progression and survival from the first metastatic manifestation. Methods: This retrospective, single center cohort study included 126 patients with breast cancer and distant metastasis treated at the University Hospital Basel, Switzerland, between 2014 and 2023. We assessed risk factors including metastatic pattern (single metastasis [SM] vs. multiple metastases [MM]), receptor status, histological subtype, and age. Disease progression from the first to second metastatic event was evaluated using the Kaplan-Meier method and log-rank test. Statistical analysis was performed using R software. Results: Patients with SM exhibited significantly better PFS compared to those with MM (HR 2.11, 95% CI 1.38–3.24). Non-triple-negative breast cancer (non-TNBC) patients had superior PFS compared to those with TNBC (HR 2.61, 95% CI: 1.53–4.44). In terms of OS, SM patients had a significantly better outcome compared to MM patients (HR 2.39, 95% CI 1.43–3.99). Additionally, non-TNBC patients showed a significantly better OS than TNBC patients (HR 3.93, 95% CI: 2.2–7). Conclusions: The extent of initial metastasis and TNBC status play a crucial role in determining prognosis in mBC. These factors are essential for predicting disease progression, guiding individualized treatment strategies, and informing ongoing discussions on optimal treatment approaches for patients with oligometastatic breast cancer.
The Best of the European Society of Gynaecological Oncology 2026 review highlights a selection of the best original research presented at the 27th Congress of the European Society of Gynaecological Oncology, held February 26 to 28, 2026, in Copenhagen, Denmark. Of the 1585 abstracts submitted, the ESGO Scientific Programme Committee chairs and authors from the European Network of Young Gynae Oncologists selected 31 high-impact studies for inclusion in this compilation. This included 10 Best Oral Sessions abstracts, 10 Mini Oral Sessions abstracts, 9 Young Investigator Session abstracts, and 2 Best 3-Minute Presentations abstracts. Key research themes this year included implementation of updated European Society of Gynaecological Oncology ovarian and endometrial cancer guidelines, refinement of surgical strategies in advanced and recurrent ovarian cancer, advances in immunotherapy and non-chemotherapy combinations, biomarker testing and personalized surgery as part of precision oncology, human epidermal growth factor receptor 2-directed therapies and antibody-drug conjugates, management of rare tumors, and innovations in prevention, diagnosis, and cervical cancer care. Through this initiative, European Society of Gynaecological Oncology and European Network of Young Gynae Oncologists aim to showcase the most impactful developments in gynaecologic oncology research and to facilitate their dissemination to clinicians, researchers, patients, advocacy groups, and allied professionals across Europe and internationally.
PURPOSE: High-dimensional tumor profiling has the potential to refine therapeutic decisions in metastatic melanoma, especially in the beyond-standard-of-care setting, but its clinical utility remains uncertain. The Tumor Profiler Study prospectively integrated multi-platform molecular, single-cell, spatial, and functional analyses into a 4-week clinical workflow. We report the biological and clinically actionable findings from the melanoma cohort. METHODS: Tumor and blood samples from 116 patients (126 tumors) underwent comprehensive profiling including CyTOF, single-cell RNA and DNA sequencing, imaging mass cytometry, proteotyping, bulk RNA/DNA sequencing, and two ex vivo drug-response platforms. Cross-modal integration defined melanoma phenotypes and identified treatment-relevant features. RESULTS: Single-cell protein profiling of 1.7 million melanoma cells identified six recurrent melanoma phenotypes present across melanoma subtypes and oncogenic drivers. Resulting tumor phenotypes stratified patients into six CyTOF-derived groups with distinct molecular characteristics and significantly different ex vivo responses to FDA-approved therapies. TYRP1-high classical melanocytic tumors showed broad drug resistance but reproducible sensitivity to cisplatin plus vindesine, consistent with elevated p53-associated DNA damage response pathways. Conversely, melanomas with heightened unfolded-protein-response activity exhibited marked sensitivity to proteasome inhibitors, supported by transcriptomic, proteomic, and functional readouts. CONCLUSION: This study establishes a clinically annotated, single-cell–resolved multi-omic atlas of advanced melanoma that links tumor phenotypes to actionable drug vulnerabilities. These findings provide a biological rationale for biomarker-driven, phenotype-guided interventional trials aimed at improving therapeutic outcomes in metastatic melanoma.
This systematic review and meta-analysis investigates the association of first-line poly(adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor) maintenance therapy with efficacy and safety outcomes among patients with advanced-stage epithelial ovarian cancer. QuestionWhat is the association of first-line poly(adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor) maintenance therapy with survival outcomes in epithelial ovarian cancer, and how do outcomes vary across regimens and subgroups?FindingsIn this meta-analysis of 7 randomized clinical trials among 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy, progression-free survival improved in most subgroups but not in homologous recombination-proficient tumors, and no subgroup demonstrated a statistically significant overall survival benefit. Efficacy and toxic effects varied across agents.MeaningThis study found that first-line PARP inhibitor maintenance therapy was associated with a progression-free survival benefit in many patient populations; however, the lack of overall survival benefit, increased toxic effects, and variability across subgroups and regimens, suggest that treatment should be individualized. ImportanceFirst-line maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARP inhibitors) after platinum-based chemotherapy improves progression-free survival (PFS) in advanced epithelial ovarian cancer (EOC), particularly in patients with BRCA-variant or homologous recombination-deficient tumors. However, overall survival (OS) benefits remain uncertain, and toxic effect profiles emphasize the need for optimized patient and agent selection.ObjectiveTo evaluate the efficacy and safety of first-line PARP inhibitor maintenance therapy compared with chemotherapy alone in advanced-stage EOC, with subgroup analyses by BRCA and HRD status, up-front or interval surgery, chemotherapy response, and residual disease.Data sourcesMedline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from database inception to August 19, 2024.Study SelectionRandomized clinical trials and prospective 2-arm studies evaluating PARP inhibitor maintenance therapy in patients with advanced-stage EOC responding to first-line platinum-based chemotherapy were included.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed in reporting this study. Data were independently extracted by 2 reviewers. Random-effects models were used for meta-analysis. Risk of bias was assessed with Cochrane risk of bias and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Main Outcomes and MeasuresPrimary outcomes were PFS and OS; secondary outcomes included high-grade adverse events.ResultsA total of 7 randomized clinical trials with 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy were included. PARP inhibitor maintenance was associated with improved PFS in the overall population (hazard ratio [HR], 0.57; 95% CI, 0.46-0.70; high certainty) and in all molecular subgroups except the homologous recombination proficient group (BRCA variant: HR, 0.40; 95% CI, 0.35-0.45; BRCA wild type: HR, 0.62; 95% CI, 0.44-0.86; homologous recombination deficient: HR, 0.44; 95% CI, 0.39-0.50; all high certainty). PFS benefits were consistent across surgical timing, chemotherapy responses, and residual disease; for example, surgical timing had HRs of 0.51 (95% CI, 0.31-0.84) for neoadjuvant chemotherapy and 0.54 (95% CI, 0.36-0.81) for primary cytoreductive surgery (all high certainty). No molecular subgroup showed a statistically significant OS improvement (high to low certainty). High-grade adverse events were more common in the PARP inhibitor group (HR, 2.40; 95% CI, 1.16-4.93; high certainty). Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib.Conclusions and RelevanceIn this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and BRCA wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions.
Quantitative phosphoproteomics enables the comprehensive analysis of signaling pathways driven by overexpressed cancer receptors, revealing the molecular mechanisms that underpin tumor progression and therapy resistance. The glycoprotein L1 cell adhesion molecule (L1CAM) is overexpressed in high-grade serous ovarian carcinoma (HGSOC) and plays a crucial role in carcinogenesis by regulating cancer stem cell properties. Here, CRISPR-Cas9-mediated knockout of L1CAM in ovarian cancer OVCAR8 and OVCAR4 cells significantly impaired anchor-independent growth in soft agar assays and reduced clonogenic survival following external beam irradiation. In vivo, L1CAM knockout decreased cancer stem cell frequency and significantly decreased tumorigenicity. To uncover L1CAM-regulated signaling networks, we employed quantitative phosphoproteomics and proteomics. Bioinformatics analyses and validation studies revealed L1CAM-associated pathways that contribute to radioresistance through DNA repair processes and mammalian target or rapamycin complex 1 (mTORC1)-mediated signaling. In conclusion, our study established a link between L1CAM-dependent tumorigenesis and radioresistance, both hallmarks of cancer stemness, with phosphorylation of key proteins involved in DNA damage response. This study further emphasizes the value of quantitative phosphoproteomics in cancer research, showcasing its ability to enhance understanding of cancer progression and therapy resistance.