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胰腺癌中的肿瘤代谢物:策略及其影响

Oncometabolites in pancreatic cancer: Strategies and its implications.

作者信息

Maiti Arunima, Mondal Susmita, Choudhury Sounetra, Bandopadhyay Arnab, Mukherjee Sanghamitra, Sikdar Nilabja

机构信息

Suraksha Diagnostics Pvt Ltd, Newtown, Rajarhat, Kolkata 700156, West Bengal, India.

Department of Zoology, Diamond Harbour Women's University, Diamond Harbour 743368, West Bengal, India.

出版信息

World J Exp Med. 2024 Dec 20;14(4):96005. doi: 10.5493/wjem.v14.i4.96005.

Abstract

Pancreatic cancer (PanCa) is a catastrophic disease, being third lethal in both the genders around the globe. The possible reasons are extreme disease invasiveness, highly fibrotic and desmoplastic stroma, dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics. This inimitable tumor microenvironment (TME) or desmoplasia with excessive extracellular matrix accumulation, create an extremely hypovascular, hypoxic and nutrient-deficient zone inside the tumor. To survive, grow and proliferate in such tough TME, pancreatic tumor and stromal cells transform their metabolism. Transformed glucose, glutamine, fat, nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism, impart therapy resistance, and immunosuppression in PanCa. Thus, a finer knowledge of altered metabolism would uncover its metabolic susceptibilities. These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa. In this review, we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.

摘要

胰腺癌(PanCa)是一种灾难性疾病,在全球范围内都是男女中致死率排名第三的疾病。可能的原因包括疾病的极端侵袭性、高度纤维化和促结缔组织增生性基质、缺乏确诊性诊断方法以及对化疗药物的耐药性。这种独特的肿瘤微环境(TME)或伴有过多细胞外基质积累的促结缔组织增生,在肿瘤内部形成了一个极度低血管、低氧和营养缺乏的区域。为了在如此恶劣的TME中存活、生长和增殖,胰腺肿瘤细胞和基质细胞会改变它们的代谢。葡萄糖、谷氨酰胺、脂肪、核苷酸代谢的改变以及肿瘤与TME之间代谢物的协同交流,赋予了胰腺癌治疗抗性和免疫抑制作用。因此更深入了解代谢改变将揭示其代谢易感性。这些独特的代谢靶点可能有助于设计新的诊断/预后标志物和治疗策略,以更好地管理胰腺癌。在这篇综述中,我们总结了胰腺癌中重塑的代谢途径,以制定针对这种毁灭性疾病的检测和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01c2/11551704/47ac444c4791/96005-g001.jpg

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