基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Breast Cancer: Molecular Pathogenesis and Targeted Therapy.
Breast Cancer: Molecular Pathogenesis and Targeted Therapy.
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乳腺癌(BC)是女性中最常见的癌症,并且仍然是全球癌症相关死亡的主要原因。其发生发展受多种因素影响,包括遗传、环境、衰老以及多种信号通路的调控。BC的异质性以及治疗耐药和复发的出现,促使研究人员探索和开发新的治疗方法。近年来,肿瘤学研究主要集中于针对BC分子异常的靶向治疗开发。这些疗法包括单克隆抗体、酪氨酸激酶抑制剂、抗体药物偶联物、PI3K/Akt/mTOR通路抑制剂、CDK 4/6抑制剂、PARP抑制剂、抗血管生成药物以及多种其他靶向药物。免疫调节策略,包括免疫检查点抑制剂(抗PD-1/PD-L1)、CTLA-4阻断剂、过继性T细胞治疗和癌症疫苗,可刺激针对癌细胞的免疫反应。表观遗传疗法如DNMT和HDAC抑制剂在BC治疗中也显示出前景。本综述强调了诸如靶向瘤内异质性、用于耐药突变检测的液体活检、旁路机制(CDK4/6抑制后FGFR1激活)、基于人工智能的药物发现、患者来源类器官以及适应性试验设计等创新方法如何塑造BC治疗。通过将分子见解与精准治疗相结合,这些进展在应对耐药、提高疗效和改善患者结局方面具有巨大潜力。
Breast cancer (BC) is the most prevalent cancer in women and remains the leading cause of cancer-related mortality globally. Its development is influenced by multiple factors, including genetics, environmental, aging, and modulation of various signaling pathways. The heterogeneity of BC together with the emergence of treatment resistance and recurrence have prompted researchers to explore and develop new therapeutic approaches. Recently, oncology research has primarily focused on the development of targeted therapies against molecular abnormalities in BC. These therapies include monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, PI3K/Akt/mTOR pathway inhibitors, CDK 4/6 inhibitors, PARP inhibitors, antiangiogenic agents, and various other targeted drugs.
Immunomodulatory strategies, including immune checkpoint inhibitors (anti-PD-1/PD-L1), CTLA-4 blockers, adoptive T-cell therapy, and cancer vaccines, stimulate immune response against cancer cells. Epigenetic therapies like DNMT and HDAC inhibitors have also shown promise in BC treatment.
This review highlights how innovative approaches like targeting intratumoral heterogeneity, liquid biopsy for resistance mutation detection, bypass mechanisms ( FGFR1 activation following CDK4/6 inhibition), artificial intelligence-based drug discovery, patient-derived organoids, and adaptive trial designs are shaping BC treatment. By combining molecular insights with precision therapeutics, these advancements offer significant potential to address resistance, improve efficacy, and enhance patient outcomes.
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