Immunoregulatory framework and the role of miRNA in the pathogenesis of NSCLC – A systematic review

Abstract

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.

Unraveling the Post-Translational Modifications and therapeutical approach in NSCLC pathogenesis

“…Various evidences suggest that the dysregulation of miRNAs contributes towards hallmarks of cancer via acting as tumor suppressor or oncogene miRNA. Our recent review has mentioned the significant role of different miRNA in NSCLC tumor microenvironment and autophagy, along with synthetic biology as a novel therapeutic approach [136] . The MRX34 (miR-34a), is the first miRNa based approach for cancer treatment which entered in phase1 clinical trials, but the trial was terminated early due to some serious adverse effects in patients [137] .…”

Mathematical Modeling Support for Lung Cancer Therapy—A Short Review

“…Of the of molecular players involved in resistance to radio-or chemotherapy ABC family transporters, EGFR, MAPK, PI3K/Akt, PTEN, NRF2, BCL-2, and FOXF1 are the most often considered subjects of research [43,44]. More and more microRNAs are found to be responsible for radio-or chemoresistance as well as altering responses to immunotherapeutic actions [45,46]. This alteration can be also used for the benefit of anticancer therapies [47].…”

Effects of PD-1, HMGB1 and LFA-1 polymorphisms on non-small cell lung cancer susceptibility

“…Among them, NSCLC accounted for about 85% of all cases [2]. There is a correlation between the diversity of some immunomodulatory genes and lung cancer susceptibility [3] As a type I transmembrane protein in the immunoglobulin (Ig) superfamily, programmed cell death protein 1 (PD-1) is mainly displayed on T cell surfaces [4]. By attenuating T-cell activation signals [5], PD-1 can help tumor cells achieve immune surveillance evasion and lead to tumor progression.…”