Mudra Sarah E, Sadhukhan Pritam, Ugurlu M Talha, Alam Shorna, Hoque Mohammad O
School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Cancers (Basel). 2021 Oct 12;13(20):5098. doi: 10.3390/cancers13205098.
Resistance to cancer therapy remains a significant obstacle in treating patients with various solid malignancies. Exposure to current chemotherapeutics and targeted agents invariably leads to therapy resistance, heralding the need for novel agents. Cancer stem cells (CSCs)-a subpopulation of tumor cells with capacities for self-renewal and multi-lineage differentiation-represent a pool of therapeutically resistant cells. CSCs often share physical and molecular characteristics with the stem cell population of the human body. It remains challenging to selectively target CSCs in therapeutically resistant tumors. The generation of CSCs and induction of therapeutic resistance can be attributed to several deregulated critical growth regulatory signaling pathways such as WNT/β-catenin, Notch, Hippo, and Hedgehog. Beyond growth regulatory pathways, CSCs also change the tumor microenvironment and resist endogenous immune attack. Thus, CSCs can interfere with each stage of carcinogenesis from malignant transformation to the onset of metastasis to tumor recurrence. A thorough review of novel targeted agents to act against CSCs is fundamental for advancing cancer treatment in the setting of both intrinsic and acquired resistance.
对癌症治疗产生耐药性仍然是治疗各种实体恶性肿瘤患者的重大障碍。接触当前的化疗药物和靶向药物总是会导致治疗耐药性，这预示着需要新型药物。癌症干细胞（CSCs）——具有自我更新和多谱系分化能力的肿瘤细胞亚群——代表了一群具有治疗抗性的细胞。癌症干细胞通常与人体干细胞群体具有相同的物理和分子特征。在具有治疗抗性的肿瘤中选择性地靶向癌症干细胞仍然具有挑战性。癌症干细胞的产生和治疗抗性的诱导可归因于几种失调的关键生长调节信号通路，如WNT/β-连环蛋白、Notch、Hippo和Hedgehog。除了生长调节通路外，癌症干细胞还会改变肿瘤微环境并抵抗内源性免疫攻击。因此，癌症干细胞可以干扰从恶性转化到转移发生再到肿瘤复发的癌症发生的各个阶段。全面回顾针对癌症干细胞的新型靶向药物对于在固有耐药和获得性耐药情况下推进癌症治疗至关重要。
