Lab for Translational Oncology and Personalized Medicine, Rashid Latif Medical College (RLMC), 35 km Ferozepur Road, Lahore, Pakistan.
Cancer Cell Int. 2012 Jun 6;12(1):22. doi: 10.1186/1475-2867-12-22.
Cancer is a multifaceted molecular disorder that is modulated by a combination of genetic, metabolic and signal transduction aberrations, which severely impair the normal homeostasis of cell growth and death. Accumulating findings highlight the fact that different genetic alterations, such as mutations in tumor suppressor genes, might be related to distinct and differential sensitivity to targeted therapies. It is becoming increasingly apparent that a multipronged approach that addresses genetic milieu (alterations in upstream and/or parallel pathways) eventually determines the response of individual tumors to therapy. Cancerous cells often acquire the ability to evade death by attenuating cell death pathways that normally function to eliminate damaged and harmful cells. Therefore impaired cell death nanomachinery and withdrawal of death receptors from cell surface are some of major determinants for the development of chemotherapeutic resistance encountered during treatment. It is therefore essential to emphasize underlying factors which predispose cells to refractoriness against TRAIL mediated cell death pathway and the relevant regulatory components involved. We bring to limelight the strategies to re-sensitize TRAIL resistant cells via vitamins to induce apoptosis.
癌症是一种多方面的分子紊乱，由遗传、代谢和信号转导异常的组合所调节，严重损害了细胞生长和死亡的正常动态平衡。越来越多的研究结果强调了这样一个事实，即不同的遗传改变，如肿瘤抑制基因的突变，可能与对靶向治疗的不同和不同的敏感性有关。显然，一种多管齐下的方法，针对遗传环境（上游和/或平行途径的改变），最终决定了个体肿瘤对治疗的反应。癌细胞经常通过减弱正常用于消除受损和有害细胞的细胞死亡途径来获得逃避死亡的能力。因此，细胞死亡纳米机械的损伤和死亡受体从细胞表面的撤出是在治疗过程中遇到的化疗耐药性发展的一些主要决定因素。因此，强调使细胞容易对 TRAIL 介导的细胞死亡途径产生抗药性的潜在因素以及涉及的相关调节成分是至关重要的。我们通过维生素来重新激活 TRAIL 耐药细胞，诱导细胞凋亡，从而突显了相关策略。
