Daya Tasvi, Breytenbach Andrea, Gu Liang, Kaur Mandeep
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, WITS, 2050 Johannesburg, South Africa.
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, WITS, 2050 Johannesburg, South Africa.
Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Mar;1870(2):159578. doi: 10.1016/j.bbalip.2024.159578. Epub 2024 Nov 13.
Pancreatic cancer remains one of the most lethal cancers due to late diagnosis and high chemoresistance. Despite recent progression in the development of chemotherapies, immunotherapies, and potential nanoparticles-based approaches, the success rate of therapeutic response is limited which is further compounded by cancer drug resistance. Understanding of emerging biological and molecular pathways causative of pancreatic cancer's aggressive and chemoresistance is vital to improve the effectiveness of existing therapeutics and to develop new therapies. One such under-investigated and relatively less explored area of research is documenting the effect that lipids, specifically cholesterol, and its metabolism, impose on pancreatic cancer. Dysregulated cholesterol metabolism has a profound role in supporting cellular proliferation, survival, and promoting chemoresistance and this has been well established in various other cancers. Thus, we aimed to provide an in-depth review focusing on the significance of cholesterol metabolism in pancreatic cancer and relevant genes at play, molecular processes contributing to cellular cholesterol homeostasis, and current research efforts to develop new cholesterol-targeting therapeutics. We highlight the caveats, weigh in different experimental therapeutic strategies, and provide possible suggestions for future research highlighting cholesterol's importance as a therapeutic target against pancreatic cancer resistance and cancer progression.
由于诊断较晚和高化疗耐药性，胰腺癌仍然是最致命的癌症之一。尽管最近在化疗、免疫治疗以及潜在的基于纳米颗粒的方法的开发方面取得了进展，但治疗反应的成功率仍然有限，而癌症耐药性进一步加剧了这一问题。了解导致胰腺癌侵袭性和化疗耐药性的新出现的生物学和分子途径，对于提高现有治疗方法的有效性和开发新疗法至关重要。一个研究不足且相对较少探索的研究领域是记录脂质，特别是胆固醇及其代谢对胰腺癌的影响。胆固醇代谢失调在支持细胞增殖、存活以及促进化疗耐药性方面具有重要作用，这在其他各种癌症中已得到充分证实。因此，我们旨在提供一篇深入综述，重点关注胆固醇代谢在胰腺癌中的重要性以及相关基因的作用、有助于细胞胆固醇稳态的分子过程，以及目前开发新的胆固醇靶向治疗方法的研究工作。我们强调了注意事项，权衡了不同的实验性治疗策略，并为未来研究提供了可能的建议，突出了胆固醇作为对抗胰腺癌耐药性和癌症进展的治疗靶点的重要性。
