Precision treatment for lung cancer

  ”Precision medicine” plays an important role in the treatment of advanced non-small cell lung cancer, with key issues: genetic abnormalities, spatial and temporal heterogeneity, treatment strategies for inert lung cancer, drug resistance, and tumor microenvironment treatment strategies.  1. Genetic abnormalities: Treatment of advanced non-small cell lung cancer can be divided into three major categories: first, patients with driver mutations; second, patients without driver mutations but pathologically identified as adenocarcinoma; and third, patients with squamous carcinoma.  The classification is very important because the treatment approaches are completely different.  For example, for patients with EGFR mutation, we give EGFR-TKI drugs; for ALK positive patients, we give ALK inhibitors; for example, for patients with ROS1 mutation, we give ROS1 inhibitors; for BRAF mutation, we give BRAF inhibitors. These are the patients that we are currently treating with very good results. It is very important to emphasize here that we do not advocate giving patients a trial of targeted drug therapy without testing.  The second major category is adenocarcinoma without detectable mutations, which is mainly treated with chemotherapy. The drugs available include traditional chemotherapy, anti-angiogenic drugs, and various antibody drugs. These patients are slightly less effective than patients with driver mutations but better than squamous epithelial carcinoma.  The third major group is squamous epithelial carcinoma. The only treatment available is conventional chemotherapy, which is not satisfactory for this group of cancers. These are the methods for the first-line clinical treatment.  2. Heterogeneity of tumor Heterogeneity includes both temporal and spatial considerations. That is, temporal heterogeneity and spatial heterogeneity. Spatial heterogeneity refers to the heterogeneity that exists at a certain point in time, including kurtosis, multi-point sampling, etc. Temporal heterogeneity is the heterogeneity that occurs as the condition changes continuously during treatment. How to overcome temporal heterogeneity will be the bottleneck for the development of precision medicine in the future.  3.Drug resistance In the process of mutual struggle between cancer cells and human body, drug resistance will appear, and after overcoming the drug resistance mechanism, new drug resistance will still be generated. However, this may turn lung cancer into a controllable chronic disease, and keep overcoming drug resistance and keep having useful drugs.  4. Microenvironment of tumor The tumor cells and the surrounding microenvironment are mutually reinforcing. The microenvironment includes anti-angiogenesis, immunotherapy, organ specificity, etc. Why are certain organs prone to metastasis? Why certain organs are prone to metastasis while others do not?  5. Inert lung cancer Clinically, some lung cancers grow very slowly and are called inert lung cancers. Does inert lung cancer need intervention and when should it be intervened? If it is identified and there is no need to intervene, and the patient is living well without symptoms and will not die, why should intervention be made? Instead, such intervention may cause undesirable consequences.