Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression and treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), contribute to tumor growth, angiogenesis, and immune evasion. Although immune cells infiltrate TME, tumor cells evade immune responses by secreting chemokines and expressing immune checkpoint inhibitors (ICIs). Vascular components, like endothelial cells and pericytes, stimulate angiogenesis to support tumor growth, while adipocytes secrete factors that promote cell growth, invasion, and treatment resistance. Additionally, perineural invasion, a characteristic feature of PDAC, contributes to local recurrence and poor prognosis. Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible factor (HIF), and Wnt/β-catenin drive tumor progression and resistance. Targeting the TME is crucial for developing effective therapies, including strategies like inhibiting CAFs, modulating immune response, disrupting angiogenesis, and blocking neural cell interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve as prognostic biomarkers and targets for personalized therapy.
胰腺导管腺癌（PDAC）因其侵袭性强、预后不良而构成重大肿瘤学挑战。肿瘤微环境（TME）在疾病进展和治疗抵抗中发挥关键作用。癌症相关成纤维细胞（CAFs）和肿瘤相关巨噬细胞（TAMs）等非肿瘤细胞通过促进肿瘤生长、血管生成和免疫逃逸参与恶性进程。尽管免疫细胞浸润TME，肿瘤细胞仍可通过分泌趋化因子和表达免疫检查点抑制剂（ICIs）逃避免疫应答。内皮细胞和周细胞等血管成分通过刺激血管生成支持肿瘤生长，而脂肪细胞分泌的因子则促进细胞增殖、侵袭和治疗抵抗。此外，PDAC特征性的神经浸润是导致局部复发和预后不良的重要因素。KRAS、TGF-β、Notch、缺氧诱导因子（HIF）及Wnt/β-catenin等关键信号通路共同驱动肿瘤进展与耐药。靶向TME对开发有效疗法至关重要，包括抑制CAFs、调节免疫应答、阻断血管生成及干预神经细胞相互作用等策略。近期多组学研究已鉴定出与失巢凋亡抵抗相关的特征基因，这些基因可作为预后生物标志物及个体化治疗靶点。
肿瘤(癌症)患者之家