Argentiero Antonella, Andriano Alessandro, Caradonna Ingrid Catalina, de Martino Giulia, Desantis Vanessa
Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
Department of Precision and Regenerative Medicine and Ionian Area, Pharmacology Section, Medical School, University of Bari Aldo Moro, 70124 Bari, Italy.
Cancers (Basel). 2024 Jul 2;16(13):2438. doi: 10.3390/cancers16132438.
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）因其侵袭性和预后不良而带来重大的肿瘤学挑战。肿瘤微环境（TME）在肿瘤进展和治疗耐药中起关键作用。非肿瘤细胞，如癌症相关成纤维细胞（CAFs）和肿瘤相关巨噬细胞（TAMs），有助于肿瘤生长、血管生成和免疫逃逸。尽管免疫细胞浸润TME，但肿瘤细胞通过分泌趋化因子和表达免疫检查点抑制剂（ICIs）来逃避免疫反应。血管成分，如内皮细胞和周细胞，刺激血管生成以支持肿瘤生长，而脂肪细胞分泌促进细胞生长、侵袭和治疗耐药的因子。此外，神经周围浸润是PDAC的一个特征，导致局部复发和预后不良。此外，包括 Kirsten 大鼠肉瘤病毒癌基因（KRAS）、转化生长因子β（TGF-β）、Notch、缺氧诱导因子（HIF）和 Wnt/β-连环蛋白在内的关键信号通路驱动肿瘤进展和耐药。靶向TME对于开发有效的治疗方法至关重要，包括抑制CAFs、调节免疫反应、破坏血管生成和阻断神经细胞相互作用等策略。最近的一种多组学方法已经鉴定出与失巢凋亡抗性相关的特征基因，这些基因可作为预后生物标志物和个性化治疗的靶点。
