Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China.
Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China.
Life Sci. 2020 Dec 15;263:118589. doi: 10.1016/j.lfs.2020.118589. Epub 2020 Oct 15.
Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and radiotherapy are the most common sarcoma treatments. However, sarcomas' response rates to chemotherapy are quite low and sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multi-drug resistance (MDR). Cancer cellular plasticity plays pivotal roles in cancer initiation, progression, therapy resistance and cancer relapse. Moreover, cancer cellular plasticity can be regulated by a multitude of factors, such as genetic and epigenetic alterations, tumor microenvironment (TME) or selective pressure imposed by treatment. Recent studies have demonstrated that cellular plasticity is involved in sarcoma progression and chemoresistance. It's essential to understand the molecular mechanisms of cellular plasticity as well as its roles in sarcoma progression and drug resistance. Therefore, this review focuses on the regulatory mechanisms and pathological roles of these diverse cellular plasticity programs in sarcoma. Additionally, we propose cellular plasticity as novel therapeutic targets to reduce sarcoma drug resistance.
肉瘤起源于间充质祖细胞干细胞，是一组预后不良的罕见恶性肿瘤。广泛的手术切除、化疗和放疗是肉瘤最常见的治疗方法。然而，肉瘤对化疗的反应率相当低，肉瘤细胞在接受化疗药物治疗后可能会产生内在或获得性耐药，导致多药耐药（MDR）的发展。癌症细胞可塑性在癌症的发生、进展、治疗耐药和癌症复发中起着关键作用。此外，癌症细胞可塑性可以通过多种因素来调节，如遗传和表观遗传改变、肿瘤微环境（TME）或治疗施加的选择性压力。最近的研究表明，细胞可塑性参与了肉瘤的进展和化疗耐药。了解细胞可塑性的分子机制及其在肉瘤进展和耐药中的作用至关重要。因此，本综述重点关注这些不同的细胞可塑性程序在肉瘤中的调控机制和病理作用。此外，我们提出细胞可塑性作为减少肉瘤药物耐药性的新治疗靶点。
