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    Item type:Publication,
    Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives
    (2026)
    Emilia Jiménez-Flores
    ;
    ;
    Dolores Jima Gavilanes
    ;
    Cesar Carrillo
    ;
    Raquel Horowitz
    Triple-negative breast cancer represents one of the most aggressive and therapeutically challenging subtypes of breast malignancies, characterized by marked biological heterogeneity, rapid progression, and limited targeted treatment options. Conventional therapies are frequently constrained by drug resistance, systemic toxicity, and high rates of recurrence. In this context, natural products have gained increasing attention as multifunctional agents capable of modulating several hallmarks of triple-negative breast cancer. Bioactive compounds, including polyphenols, terpenoids, alkaloids, and marine-derived molecules, exhibit pleiotropic antitumor effects by interfering with key oncogenic pathways. Importantly, these compounds have demonstrated the ability to counteract major mechanisms of therapeutic resistance, modulate the tumor immune microenvironment, and enhance the efficacy of standard chemotherapy and immunotherapy. Advances in drug delivery strategies, such as nanoparticle-based systems and tumor-targeted formulations, together with patient-specific molecular profiling, further expand the potential of these agents within personalized treatment approaches. This narrative review critically examines the role of natural compounds in targeting the hallmarks of triple-negative breast cancer and their potential synergistic use to improve therapeutic efficacy while reducing treatment-related toxicity. Overall, the integration of natural product-based strategies into precision oncology frameworks may offer more effective, less toxic, and individualized therapeutic options for this aggressive breast cancer subtype.
      1
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    Item type:Publication,
    Endometriosis as a Systemic and Complex Disease: Toward Phenotype-Based Classification and Personalized Therapy
    (2026) ;
    Emilia Jiménez-Flores
    ;
    Martha Montalvan
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    Raquel Horowitz
    ;
    Valeria Araujo
    Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis.
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