1 Pangaea Biotech S.L, Quirón Dexeus University Hospital, Barcelona, Spain ; 2 Santa Maria delle Croci City Hospital, Ravenna, Italy ; 3 Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 4 Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain ; 5 Fundación Molecular Oncology Research, Barcelona, Spain.
Transl Lung Cancer Res. 2016 Feb;5(1):16-25. doi: 10.3978/j.issn.2218-6751.2016.01.01.
Small cell lung cancer (SCLC) is one of the most aggressive lung tumors, with poor survival rates. Although patients may initially respond to treatment, this is followed by rapid development of drug resistance and disease progression. SCLC patients often present with metastasis at time of diagnosis, ruling out surgery as a treatment option. Currently, treatment options for this disease remain limited and platinum-based chemotherapy is the treatment of choice. A better understanding of the biology of SCLC could allow us to identify new therapeutic targets. Cancer stem cell (CSC) theory is currently crucial in cancer research and could provide a viable explanation for the heterogeneity, drug resistance, recurrence and metastasis of several types of tumors. Some characteristics of SCLC, such as aggressiveness, suggest that this kind of tumor could be enriched in CSCs, and drug resistance in SCLC could be attributable to the existence of a CSC subpopulation in SCLC. Herein we summarize current understanding of CSC in SCLC, including the evidence for CSC markers and signaling pathways involved in stemness. We also discuss potential ongoing strategies and areas of active research in SCLC, such as immunotherapy, that focus on inhibition of signaling pathways and targeting molecules driving stemness. Understanding of signaling pathways and the discovery of new therapeutic markers specific to CSCs will lead to new advances in therapy and improvements in prognosis of SCLC patients. Therefore, evaluation of these CSC-specific molecules and pathways may become a routine part of SCLC diagnosis and therapy.
小细胞肺癌（SCLC）是最具侵袭性的肺癌之一，患者生存率较差。尽管患者在初始治疗时可能会有反应，但随后会迅速产生耐药性并导致疾病进展。SCLC 患者在诊断时通常已经发生转移，排除了手术作为治疗选择。目前，这种疾病的治疗选择仍然有限，铂类化疗是首选治疗方法。对 SCLC 生物学的更好理解可以帮助我们确定新的治疗靶点。癌症干细胞（CSC）理论目前是癌症研究的关键，可以为多种肿瘤的异质性、耐药性、复发和转移提供可行的解释。SCLC 的一些特征，如侵袭性，表明这种肿瘤可能富含 CSCs，SCLC 的耐药性可能归因于 SCLC 中存在 CSC 亚群。本文总结了目前对 SCLC 中 CSC 的认识，包括 CSC 标志物和与干性相关的信号通路的证据。我们还讨论了 SCLC 中正在进行的潜在策略和活跃研究领域，如免疫疗法，这些策略和研究领域主要集中在抑制干性驱动的信号通路和靶向分子上。对信号通路的理解和对特定于 CSC 的新治疗标志物的发现将为 SCLC 患者的治疗带来新的进展和预后改善。因此，评估这些 CSC 特异性分子和途径可能成为 SCLC 诊断和治疗的常规部分。
