RESUMO
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptors, progesterone receptors and lacks HER2 overexpression. This absence of critical molecular targets poses significant challenges for conventional therapies. Immunotherapy, remarkably immune checkpoint blockade, offers promise for TNBC treatment, but its efficacy remains limited. Epigenetic dysregulation, including altered DNA methylation, histone modifications, and imbalances in regulators such as BET proteins, plays a crucial role in TNBC development and resistance to treatment. Hypermethylation of tumor suppressor gene promoters and the imbalance of histone methyltransferases such as EZH2 and histone deacetylases (HDACs) profoundly influence tumor cell proliferation, survival, and metastasis. In addition, epigenetic alterations critically shape the tumor microenvironment (TME), including immune cell composition, cytokine signaling, and immune checkpoint expression, ultimately contributing to immune evasion. Targeting these epigenetic mechanisms with specific inhibitors such as EZH2 and HDAC inhibitors in combination with immunotherapy represents a compelling strategy to remodel the TME, potentially overcoming immune evasion and enhancing therapeutic outcomes in TNBC. This review aims to comprehensively elucidate the current understanding of epigenetic modulation in TNBC, its influence on the TME, and the potential of combining epigenetic therapies with immunotherapy to overcome the challenges posed by this aggressive breast cancer subtype.
Assuntos
Epigênese Genética , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral/genética , Animais , Feminino , Imunoterapia , Metilação de DNA , Inibidores de Histona Desacetilases/uso terapêutico , Inibidores de Histona Desacetilases/farmacologiaRESUMO
Habitual expressive suppression (i.e., a tendency to inhibit the outward display of one's emotions; hereafter suppression) is often conceptualized as a maladaptive emotion regulation strategy. Yet, is this equally true for suppression of positive and of negative emotions? Across three studies and seven samples (total N > 1300 people) collected in two culturally distinct regions (i.e., Taiwan and the US), we examined the separability and distinct well-being effects of suppressing positive vs. negative emotions. Results consistently showed that (a) people suppressed their positive (vs. negative) emotions less, (b) the construct of suppression of positive (vs. negative) emotions was conceptually farther away from that of suppression of emotions in general, (c) suppression of positive and of negative emotions were only moderately correlated, and (d) only suppression of positive, but not negative, emotions, predicted lower well-being. An internal meta-analysis (k = 52 effect sizes) showed that these associations were robust to the inclusion of age, gender, and region as covariates. Future research may further probe the respective links between suppression of positive and of negative emotions and well-being across more cultural regions and across the life-span.