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Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers.

机译:针对癌症干/祖细胞以及基于干细胞的疗法:治疗和​​治愈侵袭性和复发性癌症的最终希望。

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摘要

The rapid progression from aggressive primary cancers into locally advanced and invasive and/or metastatic diseases remains a big obstacle for an early diagnosis and curative therapeutic intervention for cancer patients. The late-stage leukemias and disseminated and metastatic sarcomas, melanomas, brain tumors and epithelial cancers are the devastating diseases associated with a high rate of recurrence after treatment with the conventional clinical therapies including surgery, ionizing radiation, hormonal therapy and systemic chemotherapy, which generally lead to the death of patients. Therefore, the establishment of the molecular events underlying cancer initiation and progression into locally invasive and metastatic diseases is of major interest in basic cancer research as well as for the development of new effective clinical therapeutic options against the recurrent and lethal cancers. Recent advances have led to the identification of specific oncogenic products that are implicated in the malignant transformation of adult stem/progenitor cells into leukemic or tumorigenic and migrating cancer stem/progenitor cells during cancer progression. Of therapeutic interest, the molecular targeting of deregulated signaling elements in cancer stem/progenitor cells and their local microenvironment represents a new potential strategy for the development of more effective clinical treatments against aggressive cancers. Particularly, the combined use of chemotherapeutic drugs to eradicate cancer-initiating cells with hematopoietic stem cell or genetically-modified stem cell transplant is emerging as potential cancer treatments that hold great promise in the area of clinical cancer research. These targeting and stem cell-based therapies may offer the ultimate hope for treating and even curing the patients diagnosed with locally advanced cancers at high risk of recurrence, metastatic and/or relapsed cancers in the clinics.
机译:从侵略性原发癌快速发展成局部晚期和浸润性和/或转移性疾病仍然是癌症患者早期诊断和治疗性干预的主要障碍。晚期白血病,弥漫性和转移性肉瘤,黑色素瘤,脑瘤和上皮癌是毁灭性疾病,与常规临床疗法(包括手术,电离放射,激素疗法和全身化学疗法)治疗后复发率高相关。导致患者死亡。因此,在基础癌症研究以及针对复发性和致死性癌症的新的有效临床治疗选择的开发中,建立癌症引发和发展成局部浸润性和转移性疾病的分子事件是主要兴趣。最近的进展导致鉴定了特定的致癌产物,其与癌症发展过程中成年干/祖细胞恶性转化为白血病或致瘤和迁移的癌症干/祖细胞有关。具有治疗意义的是,癌症干/祖细胞及其局部微环境中失调的信号元件的分子靶向代表了开发针对侵袭性癌症的更有效临床治疗方法的新潜在策略。特别地,化学疗法药物与造血干细胞或基因修饰的干细胞移植的结合以根除癌症引发的细胞正在成为潜在的癌症治疗方法,在临床癌症研究领域具有广阔的前景。这些靶向和基于干细胞的疗法可能为治疗甚至治愈临床上诊断为患有局部复发癌症,复发,转移和/或复发癌症的高风险的患者提供最终希望。

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