Small-cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid proliferation, early metastasis, and frequent recurrence, which contribute to a poor prognosis. SCLC is defined by the near-universal inactivation of key tumor suppressor genes, notably TP53 and RB1, which play central roles in its pathogenesis and resistance to therapy. The p53 family of proteins, including p53, p63, and p73, is essential to maintaining cellular homeostasis and tumor suppression. TP53 mutations are almost ubiquitous in SCLC, leading to dysregulated apoptosis and cell cycle control. Moreover, p73 shows potential as a compensatory mechanism for p53 loss, while p63 has a minimal role in this cancer type. In this review, we explore the molecular and functional interplay of the p53 family in SCLC, emphasizing its members’ distinct yet interconnected roles in tumor suppression, immune modulation, and therapy resistance. We highlight emerging therapeutic strategies targeting these pathways, including reactivating mutant p53, exploiting synthetic lethality, and addressing immune evasion mechanisms. Furthermore, this review underscores the urgent need for novel, isoform-specific interventions to enhance treatment efficacy and improve patient outcomes in this challenging disease.
小细胞肺癌（SCLC）是一种高度侵袭性的恶性肿瘤，其特点是快速增殖、早期转移和频繁复发，导致预后不良。SCLC的定义性特征在于关键抑癌基因（尤其是TP53和RB1）几乎普遍失活，这些基因在其发病机制和治疗抵抗中发挥核心作用。p53蛋白家族（包括p53、p63和p73）对维持细胞稳态和肿瘤抑制至关重要。TP53突变在SCLC中几乎普遍存在，导致细胞凋亡和细胞周期调控失调。此外，p73显示出作为p53缺失补偿机制的潜力，而p63在该癌症类型中的作用较小。本综述探讨了p53家族在SCLC中的分子与功能相互作用，重点阐述其成员在肿瘤抑制、免疫调节和治疗抵抗中既独特又相互关联的作用。我们重点介绍了针对这些通路的新兴治疗策略，包括重新激活突变型p53、利用合成致死效应以及应对免疫逃逸机制。此外，本综述强调迫切需要开发新型的亚型特异性干预措施，以提高这一难治性疾病的治疗效果并改善患者预后。
Recent Research on Role of p53 Family in Small-Cell Lung Cancer
肿瘤(癌症)患者之家