Transforming cancer cells for long-term living with cancer: An inspiring new approach.

Mingjie Jiang, Dianna Gu, Furao Liu, Chenjing Lin, Ling Tian
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Abstract

Cancer is the leading cause of human death and imposes a huge health burden. Currently, no matter what advanced therapeutic modalities or technologies are applied, it is still peculiarly rare for most cancers to be radically cured whereas therapy resistance and tumor recurrence are ever so common. The long-standing cytotoxic therapy is hard to achieve long-term tumor control, and produces side-effects or even promotes cancer progression. With growing understandings of tumor biology, we came to realize that it is possible to transform but not kill cancer cells to achieve long-term living with cancer, and directly altering cancer cells is a promising way. Remarkably, tissue microenvironment is involved in the fate determination of cancer cells. Of note, leveraging cell competition to combat malignant or therapy-resistant cells shows some therapeutic potentials. Furthermore, modulating tumor microenvironment to restore a normal state might help to transform cancer cells. Especially, reprogramming cancer-associated fibroblasts, and tumor-associated macrophages, or normalization of tumor vessel, tumor immune microenvironment, and tumor extracellular matrix or their combinations, et al., revealed some long-term therapeutic benefits. Despite the massive challenges ahead, it would be possible to transform cancer cells for long-term cancer control and living with cancer longevously. The related basic researches and corresponding therapeutic strategies are also ongoing.

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转化癌症细胞长期与癌症共存:一种鼓舞人心的新方法。
癌症是人类死亡的主要原因,并造成巨大的健康负担。目前,无论采用何种先进的治疗方式或技术,大多数癌症完全治愈的情况仍然特别罕见,而耐药性和肿瘤复发却非常常见。长期的细胞毒性治疗难以实现长期的肿瘤控制,并产生副作用甚至促进癌症的进展。随着人们对肿瘤生物学的理解不断加深,我们逐渐认识到,可以转化但不能杀死癌症细胞,以实现与癌症的长期共存,直接改变癌症细胞是一种很有前途的方法。值得注意的是,组织微环境参与了癌症细胞命运的决定。值得注意的是,利用细胞竞争来对抗恶性或耐药细胞显示出一些治疗潜力。此外,调节肿瘤微环境以恢复正常状态可能有助于转化癌症细胞。特别是,对癌症相关成纤维细胞和肿瘤相关巨噬细胞进行重新编程,或使肿瘤血管、肿瘤免疫微环境和肿瘤细胞外基质正常化或其组合等,揭示了一些长期的治疗益处。尽管未来面临巨大挑战,但改造癌症细胞以长期控制癌症并长期与癌症共存是可能的。相关的基础研究和相应的治疗策略也在进行中。
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