Samarth Nikhil, Gulhane Pooja, Singh Shailza
National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune, India.
Front Oncol. 2022 Dec 21;12:1089320. doi: 10.3389/fonc.2022.1089320. eCollection 2022.
With a 5-year survival rate of only 15%, non-small cell lung cancer (NSCLC), the most common kind of lung carcinoma and the cause of millions of deaths annually, has drawn attention. Numerous variables, such as disrupted signaling caused by somatic mutations in the EGFR-mediated RAS/RAF/MAPK, PI3K/AKT, JAK/STAT signaling cascade, supports tumour survival in one way or another. Here, the tumour microenvironment significantly contributes to the development of cancer by thwarting the immune response. MicroRNAs (miRNAs) are critical regulators of gene expression that can function as oncogenes or oncosuppressors. They have a major influence on the occurrence and prognosis of NSCLC. Though, a myriad number of therapies are available and many are being clinically tested, still the drug resistance, its adverse effect and toxicity leading towards fatality cannot be ruled out. In this review, we tried to ascertain the missing links in between perturbed EGFR signaling, miRNAs favouring tumorigenesis and the autophagy mechanism. While connecting all the aforementioned points multiple associations were set, which can be targeted in order to combat NSCLC. Here, we tried illuminating designing synthetically engineered circuits with the toggle switches that might lay a prototype for better therapeutic paradigm.
非小细胞肺癌(NSCLC)是最常见的肺癌类型,也是每年数百万人死亡的原因,其5年生存率仅为15%,这引起了人们的关注。许多变量,如表皮生长因子受体(EGFR)介导的RAS/RAF/丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)、Janus激酶(JAK)/信号转导子和转录激活子(STAT)信号级联中的体细胞突变导致的信号传导中断,都以某种方式支持肿瘤的存活。在这里,肿瘤微环境通过阻碍免疫反应显著促进癌症的发展。微小RNA(miRNA)是基因表达的关键调节因子,可作为癌基因或抑癌基因发挥作用。它们对NSCLC的发生和预后有重大影响。尽管有无数种治疗方法可供使用,而且许多正在进行临床试验,但耐药性、其副作用和导致死亡的毒性仍不能排除。在这篇综述中,我们试图确定EGFR信号传导紊乱、促进肿瘤发生的miRNA和自噬机制之间缺失的环节。在连接所有上述要点时建立了多个关联,这些关联可以作为对抗NSCLC的靶点。在这里,我们试图阐明用拨动开关设计合成工程电路,这可能为更好的治疗模式奠定一个原型。