CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Drug-Resistant Epithelial Ovarian Cancer: Current and Future Perspectives.
Drug-Resistant Epithelial Ovarian Cancer: Current and Future Perspectives.
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上皮性卵巢癌(EOC)是一种复杂疾病,包含多种组织学亚型。根据侵袭性和疾病进展过程,近期通常将其分为 I 型(低级别浆液性、子宫内膜样、透明细胞和黏液性)及 II 型(高级别浆液性、高级别子宫内膜样和未分化癌)。尽管各亚型在发病机制、遗传学、预后及治疗反应方面差异显著,EOC 的临床诊断和管理在不同亚型间仍大体相似。细胞减灭术联合铂类-紫杉醇化疗,是最常见的高级别浆液性卵巢癌(HGSOC)及其他亚型的初始治疗,但多数患者存在原发或获得性耐药,且短期内复发。抗血管生成药物(如贝伐珠单抗)和用于 BRCA 突变癌症的 PARP 抑制剂等靶向疗法取得一定成功,但多种机制导致的治疗耐药仍是重大挑战。本章全面探讨应对这些挑战的新兴策略,重点介绍异常 miRNA、代谢、凋亡逃逸、癌症干细胞和自噬等因素,它们在介导 EOC 耐药和疾病复发中发挥关键作用。除标准治疗外,本研究还关注其他靶向药物,包括免疫检查点抑制剂、CAR-T 细胞和疫苗等免疫疗法,以及靶向 EOC 关键致癌通路的抑制剂。
此外,本章涵盖疾病分类、诊断、耐药通路、标准治疗及多种新兴方法的临床数据,并倡导根据个体亚型和耐药机制采取更细致、个体化的方法,以改善 EOC 各亚型患者的治疗结局。
Epithelial ovarian cancer (EOC) is a complex disease with diverse histological subtypes, which, based on the aggressiveness and course of disease progression, have recently been broadly grouped into type I (low-grade serous, endometrioid, clear cell, and mucinous) and type II (high-grade serous, high-grade endometrioid, and undifferentiated carcinomas) categories. Despite substantial differences in pathogenesis, genetics, prognosis, and treatment response, clinical diagnosis and management of EOC remain similar across the subtypes. Debulking surgery combined with platinum-taxol-based chemotherapy serves as the initial treatment for High Grade Serous Ovarian Carcinoma (HGSOC), the most prevalent one, and for other subtypes, but most patients exhibit intrinsic or acquired resistance and recur in short duration.
Targeted therapies, such as anti-angiogenics (e. g. , bevacizumab) and PARP inhibitors (for BRCA-mutated cancers), offer some success, but therapy resistance, through various mechanisms, poses a significant challenge. This comprehensive chapter delves into emerging strategies to address these challenges, highlighting factors like aberrant miRNAs, metabolism, apoptosis evasion, cancer stem cells, and autophagy, which play pivotal roles in mediating resistance and disease relapse in EOC.
Beyond standard treatments, the focus of this study extends to alternate targeted agents, including immunotherapies like checkpoint inhibitors, CAR T cells, and vaccines, as well as inhibitors targeting key oncogenic pathways in EOC.
Additionally, this chapter covers disease classification, diagnosis, resistance pathways, standard treatments, and clinical data on various emerging approaches, and advocates for a nuanced and personalized approach tailored to individual subtypes and resistance mechanisms, aiming to enhance therapeutic outcomes across the spectrum of EOC subtypes.
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