Search Results (2,528)

This systematic review examines the emerging interplay between ferroptosis and disulfidptosis, two distinct forms of regulated cell death (RCD) centered on the SLC7A11 (also known as xCT)-mediated metabolic paradox. Traditionally recognized as a potent anti-ferroptotic factor, SLC7A11 imports cystine for glutathione synthesis to neutralize iron-dependent lipid peroxidation. However, the discovery of disulfidptosis identifies SLC7A11 as a metabolic liability, representing a paradigm shift in our understanding of cellular antioxidant defense. This discovery reveals a transformative vulnerability in SLC7A11-overexpressing cells, shifting the focus from conventional survival mechanisms to the consequences of catastrophic structural collapse. Beyond metabolic exhaustion, this review highlights the role of metal dyshomeostasis as a primary driver, spanning from iron-catalyzed ferroptosis to copper-mediated metabolic interference. This conceptual framework redefines the SLC7A11 axis as a targetable “double-edged sword” in therapy-resistant malignancies. Clinical synthesis of multi-omic gene signatures, such as the disulfidptosis- and ferroptosis-related gene prognostic score (DRGPS) and the ferroptosis- and disulfidptosis-related gene (FDRG) scores, demonstrates their robust value in prognostic stratification and in predicting immunotherapy response across malignancies, including lung adenocarcinoma and hepatocellular carcinoma. Furthermore, we evaluate the capacity of disulfidptosis to prime immunogenic cell death (ICD) and remodel the immunosuppressive tumor microenvironment to bypass chemoresistance. By integrating mechanistic insights with clinical data, this review provides a comprehensive framework for targeting the SLC7A11 axis as a transformative therapeutic vulnerability in precision oncology. Full article

Background/Objectives: Bladder cancer treatment is frequently hindered by chemoresistance to agents such as cisplatin, a process in which autophagy is hypothesized to play a cytoprotective role. This study aimed to investigate the time-dependent transcriptional dynamics of autophagy-related genes in response to cisplatin in bladder cancer cell lines to better elucidate the molecular underpinnings of this resistance. Methods: Two human bladder cancer cell lines, T24 and 5637, were exposed to varying concentrations of cisplatin. Cell viability and half-maximal inhibitory concentration (IC₅₀) values were determined at 24 and 48 h using the MTS assay. Subsequently, the relative mRNA expression levels of key autophagy-related genes (ULK1, BECN1, ATG5, ATG7, LC3B, SQSTM1/p62, LAMP1, and TFEB) were quantitatively analyzed via RT-qPCR at 0, 6, 24, and 48 h intervals. Results: Cisplatin exerted a dose- and time-dependent cytotoxic effect, with 5637 cells exhibiting significantly greater sensitivity compared to T24 cells. Transcriptional analysis revealed a dynamic, multiphasic modulation of the autophagic pathway: an early-phase upregulation of initiation genes (ULK1, BECN1), a mid-phase increase in autophagosome formation genes (ATG5, ATG7), and a late-phase alteration in lysosomal regulation genes (LAMP1, TFEB). Notably, the more chemoresistant T24 cells mounted a robust and sustained autophagic transcriptional response, whereas the sensitive 5637 cells demonstrated a more limited and transient reaction. Conclusions: Cisplatin modulates the autophagic pathway at the transcriptional level in a highly dynamic, time-dependent, and cell-line-specific manner. Interpreted alongside established functional evidence in the literature, the sustained autophagic gene expression observed in the resistant cells is consistent with a potential cytoprotective role, warranting further functional validation at the protein level. These findings map the temporal genetic landscape of cisplatin-induced autophagy, providing a theoretical framework for optimizing the timing of autophagy-targeted combination therapies in bladder cancer. Full article

Hematological malignancies, including multiple myeloma (MM), leukemia, and lymphoma, represent a major global health burden, accounting for approximately 6.6% of all cancer cases and contributing to significant mortality. The evolutionary conserved WNT/β-catenin signaling pathway is a critical regulator of normal hematopoietic stem cell homeostasis, and its dysregulation is a hallmark of various hematological malignancies. Aberrant activation through mutations, overexpression of ligands, or disruption of the destruction complex drives uncontrolled proliferation, impaired differentiation, and therapeutic resistance to therapy in acute and chronic leukemias, lymphomas, and multiple myeloma. Therapeutic interventions targeting this pathway, such as GSK-3 inhibitors, β-catenin antagonists, and small molecules like CWP291 and salinomycin, have demonstrated promising antitumor effects. Furthermore, combining WNT/β-catenin inhibition with targeted or epigenetic therapies, such as venetoclax and chidamide, can produce synergistic antitumor effects and overcome chemoresistance. Despite this potential, clinical translation is hampered by on-target toxicities in healthy tissues, pathway complexity, and a lack of predictive biomarkers. We conclude that the future of WNT-directed therapy lies in developing biomarker-selective agents, advanced drug delivery systems to improve specificity, and exploring novel combinations with immunotherapy to harness the anti-tumor immune response. Full article

Glioblastoma (GB) classical treatment with the alkylating drug temozolomide (TMZ) is not effective mainly due to chemoresistance mechanisms, particularly those mediated by O6-methylguanine-DNA methyltransferase (MGMT). In this context, polyethylene glycol (PEG)-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed to deliver tamoxifen (TAX), a clinically approved non-alkylating drug with reported anti-GB activity. The NP formulation was optimized using a factorial design and subsequently functionalized with lactoferrin (Lf) to enhance GB targeting. The Lf-conjugated optimized formulation exhibited a mean diameter of 193 ± 6 nm, a polydispersity index (PDI) of 0.11 ± 0.04, a zeta potential of −18.2 ± 6.8 mV, and an encapsulation efficiency (EE) of 68.6 ± 1.8%. The NPs exhibited a sustained release profile for up to 23 days, and remained stable under physiological conditions. Cell uptake studies, conducted in human GB cells (U87, U251, and T98G) and healthy astrocytes, demonstrated enhanced internalization of Lf-NPs in GB cells compared with non-conjugated NPs, suggesting uptake through Lf-binding site-mediated endocytosis. Cytotoxicity assays further indicated that Lf-conjugation improved the antiproliferative efficacy of TAX-loaded NPs relative to non-functionalized formulations, particularly in GB cells. Moreover, combination studies with TMZ showed that the developed NPs were able to sensitize GB cells to treatment with this alkylating agent. In sum, this work supports the potential of the developed Lf-decorated TAX-loaded PLGA NPs as a nanoplatform for targeted delivery against GB. Full article

Background: Photodynamic therapy (PDT) has emerged as a powerful minimally invasive modality for cancer treatment. However, its efficacy as a monotherapy is often limited by oxygen dependence and limited light penetration. Combining PDT with systemic anticancer drug therapies offers a promising strategy to achieve synergistic effects and overcome resistance. Objective: This review aims to provide a systematic analysis of the mechanisms and clinical potential of combining PDT with chemotherapy, targeted therapy, and immunotherapy, focusing on recent advancements and nanotechnology-based delivery systems. Methods: A comprehensive literature search was performed using PubMed and Scopus databases. The analysis focused on peer-reviewed studies published over the last 10 years addressing synergistic molecular pathways, co-delivery nanoplatforms, and clinical trial outcomes. Results: The combination of PDT with chemotherapy enhances drug accumulation via vascular photosensitization and can overcome multi-drug resistance. Integration with immunotherapy, particularly immune checkpoint inhibitors and tumor vaccines, triggers immunogenic cell death (ICD), leading to systemic antitumor responses. Nanotechnology provides a versatile platform for the targeted co-delivery of photosensitizers and pharmacological agents, significantly reducing systemic toxicity. Conclusions: Combined PDT–drug regimens demonstrate superior therapeutic efficacy compared to monotherapies. Future clinical translation requires the standardization of dosimetry and the development of multifunctional nanomedicines to enable personalized treatment protocols. Full article

Triple-negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat, defined by its molecular heterogeneity, absence of hormone receptors, and poor clinical outcomes. While this difficulty with cancer cells persists even in the presence of chemotherapy and immune checkpoint inhibitors (ICIs), one critical factor linked to both chemoresistance and immune escape is autophagy. Autophagy is a cellular process with lysosomal recycling function. In TNBC, autophagy paradoxically shifts from tumor-suppressive to a tumor-promoting role. Autophagy was initially known to maintain genomic stability and alleviate oxidative damage. In TNBC, cancer cells use autophagy to detoxify platinum-induced DNA. damage, clear damaged mitochondria via mitophagy, recycle critical macromolecules, and sustain dormancy in cancer stem-like cells (CSCs). At the same time, the process of autophagic flux facilitates immune evasion, including PD-L1 expression stabilization, MHC-I degradation, and the establishment of an immunosuppressive tumor microenvironment (TME). The review encapsulates the progressive concepts of molecular regulation of autophagy, which involve key factors such as ULK1, VPS34, and non-coding RNAs (ncRNAs). These factors play a significant role in chemoresistance, taxanes, anthracyclines, and platinum compounds. The review also discusses various strategies for translation that aim to circumvent or suppress autophagy-mediated chemoresistance, including autophagy inhibitors, natural compounds, and nanoparticle-based formulations, with a focus on their synergistic potential with ICIs and chemotherapeutic agents. Targeting autophagy has shown considerable potential for effectively addressing chemoresistance in TNBC. Future studies should focus on addressing chemoresistance and immunoresistance through autophagy-based therapies. Full article

Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive Epstein–Barr virus (EBV)-associated lymphoma characterized by intrinsic chemoresistance and an immunosuppressive tumor immune microenvironment (TIME). EBV-driven immune dysregulation provides a biological rationale for immunotherapy. This review summarizes current advances in immunotherapeutic strategies for NKTCL, integrating molecular mechanisms, clinical evidence, and resistance mechanisms within the context of TIME remodeling and immune reprogramming. We synthesize evidence from clinical trials, translational studies, and preclinical investigations evaluating immune checkpoint inhibitors, antibody-based therapies, adoptive cellular therapies, immune engagers, EBV-directed immunotherapies, and multimodal combination strategies in NKTCL. Among these strategies, PD-1/PD-L1 inhibitors are the most extensively studied immunotherapies in NKTCL and demonstrate clinically meaningful activity across different clinical settings. However, therapeutic responses remain heterogeneous, and primary or acquired resistance is common, driven by EBV-associated immune suppression, defective antigen presentation, metabolic reprogramming, and multi-checkpoint co-expression. Beyond immune checkpoint blockade, emerging approaches—including dual-checkpoint inhibition, epigenetic and metabolic combinations, antibody–drug conjugates, EBV-specific cytotoxic T lymphocytes, chimeric antigen receptor (CAR)-based platforms, immune engagers, and EBV vaccines—have shown encouraging signals in early-phase studies. Increasing evidence also supports multimodal strategies integrating immunotherapy with radiotherapy and other immune-modulatory interventions to enhance immune reprogramming and improve response durability. Overall, immunotherapy has substantially expanded the therapeutic landscape of NKTCL but remains constrained by complex EBV–TIME interactions and interpatient heterogeneity. Future progress will rely on biologically informed patient stratification, rational multimodal combination strategies, and integration of innovative immune platforms to establish a durable, immune-reprogramming-centered treatment paradigm for EBV-driven NKTCL. Full article

Dickkopf-1 (DKK1) is a 266-amino-acid secreted glycoprotein originally identified as a high-affinity antagonist of the canonical Wnt/β-catenin signaling pathway and has emerged as a complex regulator in oncology. While historically considered as a tumor suppressor due to its ability to abrogate Wnt-driven proliferation, recent discoveries highlight a paradoxical pro-oncogenic role across various malignancies. The molecular mechanisms by which DKK1 promotes tumor progression, metastasis, and immune evasion are driven by its interaction with cell-surface receptors, specifically LRP5/6 and CKAP4. The DKK1-CKAP4 axis independently activates PI3K/AKT signaling, facilitating epithelial–mesenchymal transition (EMT), chemoresistance, and the formation of osteolytic bone lesions. Furthermore, DKK1 serves as a critical orchestrator of the tumor microenvironment (TME) by driving comprehensive immune reprogramming. It mediates the recruitment of myeloid-derived suppressor cells (MDSCs) and inactivates cytotoxic CD8⁺ T cells and natural killer (NK) cells, thereby fostering an immunosuppressive tumor microenvironment and resistance to checkpoint inhibitors. Interestingly, cancer-associated fibroblasts (CAFs) are a primary source of DKK1 in the stroma, where they facilitate immune evasion. Clinically, elevated circulating DKK1 levels correlate with advanced disease stages, increased metastatic potential, and poor overall survival in solid and hematological tumors. When used in combination with established biomarkers, serum DKK1 levels demonstrate significant utility for early detection and therapeutic monitoring. Given its intricate impact on malignancy, DKK1 has become a promising therapeutic target, with ongoing clinical trials investigating neutralizing antibodies such as DKN-01 to disrupt its oncogenic and immunosuppressive signaling. Understanding the context-dependent nature of DKK1 signaling remains essential for refining its application as both a biomarker and a component of emerging precision immunotherapy strategies. By prioritizing the literature from the last decade, this review characterizes DKK1 as a key mediator of tumor progression and immune reprogramming, while assessing its clinical potential as a biomarker and therapeutic target. Full article

Objective: We evaluated whether a deep-learning model could predict the response to neoadjuvant chemotherapy (NAC) in breast cancer using the pre-treatment B-mode ultrasound. Methods: This retrospective study included 245 female patients (253 lesions) treated with NAC between 2017 and 2019. Lesions were categorized as complete response (CR; 103) or non-CR (150) based on postoperative pathology. We trained ResNet18-based models using pre-treatment B-mode ultrasound images (Image) and clinical features. Three training strategies were evaluated: training from scratch (SC); transfer learning (TL); and domain-specific pretraining (USP). Predictive performance was assessed using descriptive statistics. Results: The best-performing model (USP Image) achieved 0.76 accuracy (specificity: 0.80; sensitivity: 0.72), significantly outperforming all other models, including those that used additional clinical features ($p<0.05$). USP improved performance across most model types compared to SC and TL, highlighting the value of domain-specific pretraining. Clinical features added value with SC or TL, but not with USP, suggesting that pretrained models can extract the most relevant information directly from images. Grad-CAM analysis revealed that non-CR predictions focused on the tumor and posterior shadowing—features linked to chemoresistant subtypes. CR predictions focused mainly on more heterogeneous, peritumoral regions. Conclusion: This finding underscores ultrasound’s potential as a low-cost, accessible tool for predictive oncology in personalized, AI-driven treatment planning. Full article

Background/Objectives: The clinical management of bladder cancer is severely impeded by high recurrence rates and the rapid emergence of chemoresistance, necessitating the discovery of novel therapeutic agents with distinct mechanisms of action. Dehydrodiisoeugenol (DHE), a bioactive neolignan, exhibits potent anti-tumor efficacy, yet its direct molecular targets and mode of action remain elusive. Methods: To deconvolute the mechanism of DHE, we integrated a phenotypic screening approach using 2D cell lines and 3D patient-derived organoids with a chemoproteomics-based activity-based protein profiling (ABPP) strategy. We synthesized a functionalized photoaffinity probe to capture the specific interactome of DHE under physiological conditions and validated targets via cellular thermal shift assays (CETSA), quantitative mass spectrometry, and 100 ns molecular dynamics (MD) simulations. Results: DHE exhibited potent dose-dependent cytotoxicity in bladder cancer cells, with IC50 values of 39.23 μM in T24 and 34.58 μM in 5637 cells. In 3D patient-derived organoids, DHE significantly reduced viability (p < 0.0001). Using a dual-filtering ABPP strategy, we identified 65 high-confidence candidate targets, prioritizing PTPN1 (PTP1B) as the primary functional interactor. Comparative molecular docking and 100 ns MD analyses showed that multiple stereoisomers of DHE could adopt plausible PTPN1-binding modes. Mechanistically, organoid proteomics indicated that DHE engagement with PTPN1 disrupts ER membrane homeostasis, thereby modulating the PI3K-Akt signaling axes. Conclusions: These findings establish PTPN1 as a critical druggable vulnerability in bladder cancer and define the molecular basis for the therapeutic potential of DHE. This study highlights the power of combining chemoproteomics with physiological 3D models to accelerate the translation of natural products into precision cancer therapies. Full article

Background: Bone metastasis is a major determinant of morbidity and therapeutic failure in advanced prostate cancer (PCa); however, the transcriptional programs and tumor microenvironmental alterations driving metastatic progression remain incompletely understood. This study aimed to systematically characterize transcriptomic differences between non-metastatic and bone-metastatic PCa and to identify key microenvironmental signaling pathways involved in tumor survival and chemoresistance. Methods: Bulk RNA sequencing was performed on 49 non-metastatic and 28 bone-metastatic PCa specimens. Differential expression analysis was integrated with weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis, and immune/stromal deconvolution. Key findings were validated using in vitro functional assays, including Transwell co-culture models, small interfering RNA (siRNA)-mediated gene silencing, cell viability, apoptosis, and docetaxel resistance analyses. Results: Transcriptomic profiling identified 574 differentially expressed genes. Bone-metastatic tumors were enriched in ribosome-related and translational pathways, whereas non-metastatic tumors displayed immune-associated signatures, including natural killer (NK) cell-mediated cytotoxicity and cytokine signaling. WGCNA revealed immune-related gene modules preferentially enriched in non-metastatic disease. Immune deconvolution demonstrated significantly higher infiltration of NK cells and endothelial cells in non-metastatic tumors. Chemokine-receptor analysis highlighted upregulation of the CXCL10-CXCR3 axis in non-metastatic PCa. In vitro, PCa cells expressed CXCR3, while endothelial cells markedly increased CXCL10 expression upon co-culture. Functional assays showed that endothelial-derived CXCL10 promoted PCa cell survival, suppressed apoptosis, and conferred resistance to docetaxel via CXCR3-dependent signaling; these effects were reversed by CXCL10 or CXCR3 knockdown. Conclusions: These findings uncover a context-dependent endothelial-immune chemokine network distinguishing non-metastatic from bone-metastatic PCa and identify the CXCL10-CXCR3 axis as a critical mediator of tumor survival and chemoresistance, suggesting a potential therapeutic vulnerability in advanced prostate cancer. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Patients are treated with DNA damaging chemotherapies which act by inducing DNA damage in rapidly dividing tumor cells. Unfortunately, these tumors frequently develop treatment resistance, underscoring the need to understand resistance mechanisms in order to develop better treatment strategies. DNA damage response (DDR) detects and repairs DNA damage, and the DDR pathway has been shown to contribute to chemoresistance. Another factor known to drive chemoresistance in PDAC is the dense stroma, composed of extracellular matrix proteins secreted by cancer-associated fibroblasts (CAFs). Our recent work identified a CAF-induced resistance mechanism involving N-myc downstream regulated gene 1 (NDRG1). CAF-induced signaling resulted in the phosphorylation of NDRG1 and NDRG1-dependent DNA repair and protection from chemotherapies. Loss of NDRG1 resulted in increased chemotherapy-induced DNA damage and decreased replication fork speed and recovery. Methods: To gain insight into the molecular mechanism of NDRG1-mediated DNA repair and replication, we performed a BioID screen to identify binding partners of NDRG1. We further assessed the mechanistic roles of the identified interaction partners on DNA repair using DNA replication and repair assays such as the Comet assay and DNA fiber assays. Results: Our BioID screen identified meiotic recombination 11 (MRE11) protein, a nuclease involved in DDR, as a putative NDRG1 interacting protein. Interaction between MRE11 and NDRG1 was enriched during the late S/early G2 cell cycle phases and under replication stress. However, this interaction is likely indirect as the interaction only occurred in a cellular context and not with in vitro purified proteins. Blocking NDRG1 phosphorylation or blocking MRE11 exonuclease activity both resulted in protection of newly synthesized DNA at stalled replication forks. In NDRG1 knockout cells, blocking MRE11 led to decreased protection of nascent DNA, suggesting that NDRG1 and MRE11 may be acting in the same pathway and that NDRG1 is required for MRE11’s activity at stalled forks. Conclusions: In summary, our work has uncovered a protein complex between NDRG1 and MRE11 that may play a key role in chemoresistance due to its role in the processing of stalled replication forks. Full article

Background/Objectives: Claudin-6 (CLDN6) is an oncofetal tight junction protein that has recently emerged as a promising therapeutic target in various solid tumors. Despite this potential, the clinical significance of CLDN6 expression in advanced-stage high-grade serous ovarian carcinoma (HGSC)—specifically its role in platinum resistance—remains poorly understood. Methods: This retrospective study analyzed 119 patients with newly diagnosed FIGO stage III–IV HGSC who received platinum-based chemotherapy at a single tertiary center between 2015 and 2025. CLDN6 expression was evaluated via immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tumor samples. High CLDN6 expression was defined as moderate-to-strong membranous staining in ≥50% of tumor cells. Clinicopathologic associations were assessed using chi-square tests, while logistic regression analysis identified predictors of platinum resistance. Finally, overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan–Meier methods and Cox proportional hazards models. Results: High CLDN6 expression was observed in 31 patients (26%). CLDN6 expression was not significantly associated with age, CA-125 level, lymph node metastasis, distant metastasis, surgical approach, or residual disease status. However, high CLDN6 expression was significantly associated with platinum resistance (61.3% vs. 28.4%, p = 0.001). In multivariable logistic regression analysis, residual disease (OR = 10.12, p > 0.001), high CLDN6 expression (OR = 4.52, p = 0.008), and elevated CA-125 levels (OR = 0.64, p = 0.041) were independently associated with platinum resistance. Median OS for the entire cohort was 43.8 months. High CLDN6 expression was associated with shorter OS (38.0 vs. 45.7 months, p = 0.042) and remained an independent predictor of mortality in multivariable Cox analysis (HR = 1.90, p = 0.026). CLDN6 expression showed a trend toward shorter PFS but did not reach statistical significance (p = 0.096). Conclusions: High CLDN6 expression is associated with platinum resistance and inferior overall survival in patients with advanced-stage HGSC. These findings suggest that CLDN6 may serve as a clinically relevant biomarker for chemoresistance and tumor aggressiveness. In the context of emerging CLDN6-targeted therapies, routine assessment of CLDN6 expression may facilitate the development of biomarker-driven therapeutic strategies for advanced ovarian cancer. Full article

Nucleoside analogs (NAs) play a central role in cancer therapy, either through direct cytotoxicity or epigenome reprogramming. They are clinically effective but have shortcomings in their long-term effectiveness because of variable patient responses and the emergence of resistance. There is growing evidence that DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (ncRNAs) are key factors that determine sensitivity and resistance to NAs. This review summarizes existing evidence on the epigenetic control of cytotoxic and epigenetic nucleoside analogs, discusses predictive biomarkers of human Equilibrative Nucleoside Transporter 1 (hENT1) and deoxycytidine kinase (dCK) promoter methylation, histone modifications, and ncRNA signatures, and assesses the emerging strategies of multi-omic integration. Improvements in detection methods, such as high-resolution sequencing, single-cell profiling, and liquid biopsy, are addressed, along with the issues of reproducibility, tumor heterogeneity, and clinical translation. Epigenetic biomarkers are promising for patient stratification in clinical trials, although a lack of uniformity in technical and methodological approaches currently constrains their full potential. The future focus will be on standardized panels of biomarkers, real-time monitoring, rational combination strategies, and biomarker-directed clinical trial designs. Overall, epigenetic biomarkers are capable of changing nucleoside analog therapy into a more precise, durable, and personalized treatment approach. Full article

Endometriosis is a chronic estrogen-dependent disorder affecting approximately 10% of women of reproductive age. Increasing epidemiological and molecular evidence indicates that it may represent a precursor condition for a subset of ovarian malignancies collectively defined as endometriosis-associated ovarian cancer (EAOC), predominantly endometrioid and clear cell carcinomas. Malignant transformation is driven by the interplay between chronic inflammation, oxidative stress, and local hyperestrogenism within the endometriotic microenvironment. Recurrent hemorrhage and persistent immune activation further promote genomic instability and clonal expansion. Shared somatic mutations have been identified in both atypical endometriosis and adjacent carcinomas, supporting a model of stepwise tumorigenesis. Dysregulation of signaling pathways and epigenetic mechanisms, including microRNA alterations, further contribute to tumor development. Although the absolute risk of malignant transformation remains low, women with ovarian endometriosis and deep infiltrating disease show an increased risk of ovarian cancer. EAOC is frequently diagnosed at earlier stages and generally demonstrates a more favorable prognosis than high-grade serous carcinoma, although clear cell histotypes may exhibit chemoresistance and distinct molecular vulnerabilities. This review summarizes current evidence on the pathogenesis, molecular mechanisms, and clinical implications of EAOC, highlighting future strategies for risk stratification and personalized surveillance. Full article