Szymonik Julia, Wala Kamila, Górnicki Tomasz, Saczko Jolanta, Pencakowski Bartosz, Kulbacka Julita
Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2021 Dec 22;23(1):89. doi: 10.3390/ijms23010089.
Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells' maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.
肿瘤性疾病仍然是一项重大的医学挑战,需要不断寻找新的治疗方案。许多癌症的一个严重问题是对抗癌药物产生耐药性以及在转移或局部复发时疾病进展。癌细胞的这些特性可能与癌症干细胞(CSC)的特定属性有关。癌症干细胞参与抑制细胞成熟,这对于维持其自我更新能力和多能性至关重要。它们显示出转录因子蛋白的表达增加,这些蛋白被定义为与干性相关的标志物。这组蛋白包括OCT4、SOX2、KLF4、Nanog和SALL4。人们已经注意到癌细胞的代谢发生了变化,对铁的需求显著增加。铁螯合剂已被证明具有抗肿瘤活性,并影响与干性相关标志物的表达,从而降低化疗耐药性和肿瘤细胞进展的风险。这促使人们进一步研究这些药物作为有前景的新型抗癌药物。本文介绍了干性标志物的特征及其对肿瘤性疾病发展和进程的影响。还描述了现有的铁螯合剂,并分析了它们对癌细胞和与干性相关标志物表达的影响。