A Model Of NSCLC Microenvironinent Predicts Optimal Receptor Targets

In recent years,lung cancer has gradually become the leading cause of death of malignant tumors in cities of China,with high morbidity and mortality.Despite significant progression in the development of anti-tumor therapy,including immunotherapy and targeted therapy,acquired drug resistance is still a typical phenomenon during treatment that results in the failure.The resistance is incubated in and highly dependent on tumor microenvironment,however,the mechanisms underlying the phenomenon are incompletely understood.Therefore,understanding how tumor cells co-evolve with tumor-associated immune cells and stromal cells is important for tumor treatment.Tumor cells may bypass the circuits that were regulated by drug and rebuild their superior fitness by reconstructing the topology of the intercellular signaling network.To tackle this challenge,we established a logistic population dynamics model to describe the growth dynamics and fitness of cells in terms of cell-cell communications in non-small-cell lung cancer.Based on the model,we simulated and analyzed the effects of traditional therapy(surgery,radiotherapy and chemotherapy)and targeted therapy on virtual patients.Besides,inspired by the shooting sport with running targets,we proposed a tracking targeted therapeutic strategy to effictively overcome acquired drug resistanceThe results obtained show that tumor cells always remained positive fitness,and paracrine in tumor microenvironment played an important role in the development of cancer.As for targeted therapy,the synergistic effect when inhibiting multiple signaling pathways may help significantly retard carcinogenic processes associated with disease progression,compared with suppression of a single signaling pathway.And the combination of traditional and targeted therapy,as an interesting experiment,was significantly more effective in treatment of virtual patients due to a clear complementary relationship between the two therapeutic schemes.A novel targeting strategy,tracking targeted therapy developed from multi-target therapy shows good efficacy in patients with dramatic changes in physical condition and acquired drug resistance,and provides the potential for long-term disease control.