Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, C R Avenue, Kolkata, West Bengal 700073, India.
Int J Biochem Cell Biol. 2018 Oct;103:115-124. doi: 10.1016/j.biocel.2018.08.011. Epub 2018 Aug 25.
Chemoresistance to the anticancer therapy is the main challenge for the recurrence of cancer and it is responsible for treatment failure and unfavorable clinical outcome. Understanding the mechanisms of chemoresistance in cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last few decades, cancer stem cells (CSC) have proven to play a key role in tumor initiation and may also act as a key factor for chemoresistance and recurrence of the disease following chemotherapy. Resistance to anticancer therapy in patients has been attributed towards a number of factors controlling the stemness character of the cancer stem cells which leads to therapeutic resistance. Accumulating evidences show that the bone marrow (BM) niche is critical to the maintenance and retention of cancer stem cells. Undeniably, stromal cells within the BM niche provide a sanctuary where different signaling pathways and cell-cell interaction gives a protective nature to the diseased condition, and thereby evade chemotherapy-induced death. In this review we have tried to highlight the factors which have important role in chemoresistance and are associated with bone marrow microenvironment. We have also discussed about the recent progresses regarding CSC-targeted therapies to throw light toward developing more effective therapeutic strategies to eradicate cancer in the patients concerned.
癌症的化疗耐药性是癌症复发的主要挑战,它导致了治疗失败和不良的临床结局。了解癌症化疗耐药性的机制有助于预测疾病进展、开发新的治疗方法和实现个体化的系统治疗。在过去的几十年中,癌症干细胞(CSC)已被证明在肿瘤起始中起关键作用,并且可能也是化疗后疾病耐药和复发的关键因素。患者对抗癌治疗的耐药性归因于控制癌症干细胞干性特征的许多因素,导致治疗耐药性。越来越多的证据表明,骨髓(BM)龛对于维持和保留癌症干细胞至关重要。不可否认的是,BM 龛中的基质细胞为不同的信号通路和细胞-细胞相互作用提供了一个避难所,使疾病状态具有保护性质,从而逃避化疗诱导的死亡。在这篇综述中,我们试图强调在化疗耐药性中起重要作用并与骨髓微环境相关的因素。我们还讨论了关于 CSC 靶向治疗的最新进展,以期为开发更有效的治疗策略以根除相关患者的癌症提供思路。