Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
Adv Cancer Res. 2016;131:159-91. doi: 10.1016/bs.acr.2016.04.003. Epub 2016 Jun 3.
Cancer is a multifactor and multistep process that is affected intrinsically by the genetic and epigenetic makeup of tumor cells and extrinsically by the host microenvironment and immune system. A key component of cancer involves a unique subpopulation of highly malignant cancerous cells referred to as cancer stem cells (CSCs). CSCs are positioned at the apex of the tumor hierarchy with an ability to both self-renew and also generate non-CSC/differentiated progeny, which contribute to the majority of the tumor mass. CSCs undergo functional changes and show plasticity that is stimulated by specific microenvironmental cues and interactions in the tumor niche, which contribute to the complexity and heterogeneity of the CSC population. The prognostic value of CSCs in the clinic is evident since there are many examples in which CSCs serve as markers for poor patient prognosis. CSCs are innately resistant to many standard therapies and they display anoikis resistance, immune evasion, tumor dormancy, and field cancerization, which may result in metastasis and relapse. Many academic laboratories and biotechnology companies are currently focusing on strategies that target CSCs. Combination therapies, epigenetic modifiers, stemness inhibitors, CSC surface marker-based therapies, and immunotherapy-based CSC-targeting drugs are currently undergoing clinical trials. Potential new targets/strategies in CSC-targeted therapy include MDA-9/Syntenin (SDCBP), Patched (PTCH), epigenetic targets, noncoding RNAs, and differentiation induction. Defining ways of targeting and destroying CSCs holds potential to impact significantly on cancer therapy, including prevention of metastasis and cancer recurrence.
癌症是一个多因素、多步骤的过程，内在受到肿瘤细胞遗传和表观遗传构成的影响，外在受到宿主微环境和免疫系统的影响。癌症的一个关键组成部分涉及到一种被称为癌症干细胞（CSC）的高度恶性癌细胞的独特亚群。CSC 位于肿瘤层次结构的顶端，具有自我更新和产生非 CSC/分化后代的能力，这些后代有助于肿瘤的大部分生长。CSC 经历功能变化并表现出可塑性，这是由肿瘤生态位中特定的微环境线索和相互作用刺激的，这有助于 CSC 群体的复杂性和异质性。CSC 在临床中的预后价值是明显的，因为有许多例子表明 CSC 是患者预后不良的标志物。CSC 对许多标准疗法具有固有抗性，并且它们表现出抗凋亡、免疫逃避、肿瘤休眠和场癌变，这可能导致转移和复发。许多学术实验室和生物技术公司目前都专注于针对 CSC 的策略。联合疗法、表观遗传修饰剂、干细胞抑制剂、CSC 表面标志物为基础的疗法和基于免疫疗法的 CSC 靶向药物目前正在进行临床试验。CSC 靶向治疗的潜在新靶点/策略包括 MDA-9/Syntenin（SDCBP）、 patched（PTCH）、表观遗传靶点、非编码 RNA 和分化诱导。确定靶向和破坏 CSC 的方法有可能对癌症治疗产生重大影响，包括预防转移和癌症复发。
