Clinic Advances in Non-Small-Cell Lung Cancer

Dear Colleagues,

Non-small-cell lung cancer (NSCLC), which accounts for 85% of lung cancer cases, is clinically presented as a plethora of genetically mutated tumors. The novel research associated with detecting specific DNA alterations has led to the discovery of drugs which are able to target gene variants. Treating patients with lung cancer is a challenge due to late-stage diagnosis and thus high mortality. An active approach with early screening will increase patient survival rates by offering the molecular profiling of tumor biopsy, hence targeting individual proteins such as inhibiting Tyrosine Kinase. Immunotherapy using immune checkpoint inhibitors (ICI) aims to block PD and PD-L1 proteins associated with balancing the immune system activity, hence allowing a stronger anticancer immune response. Examples of ICIs approved by the FDA as adjuvant and neoadjuvant agents provide first and second lines of treatments, including consolidation, are Atezolizumab, Cemiplimab, Durvalumab, Nivolumab, and Pembrolizumab. In addition, NSCLC-accepted therapies use inhibitors to attack certain cancer cells with ALK alterations, which tend to have disease progression in the brain. Among the recent pharmaceutical agents are Alectinib, Brigatinib, and Lorlatinib. ROS1 mutated gene in NSCLC makes changes in cell signalling affecting cell growth. To counteract the ROS1 protein, crizotinib and entrectinib are used for treating these patients. Moreover, to decrease the spread and growth of NSCLC cells, a combination of the drugs trametinib, acting on kinase proteins called MEK and dabrafenib, and inhibiting B-Raf involvement in cellular signal transduction is used to treat certain patients. Blocking EGFR function is important to stop the abnormally high division activity linked to this receptor through administering Osimertinib, Gefitinib, Erlotinib, Dacomitinib, and Afatinib. Ongoing clinical trials address several issues expressed by NSCLC patients, among them CNS metastases and resistance to TKI. Recent studies show emerging encouraging results of drug combinations emphasizing the clinician’s discretion to be aware of the medical publications allowing them to tailor the best care and drug of choice available to each patient.

The present Special Issue aims to explore “Clinic Advances in Non-Small-Cell Lung Cancer” by compiling the most significant recent breakthroughs in the topics concerning novel drug development and updated therapeutic applications. The highlights sections are:

1. Early detection involving low-dose CT scans for heavy smokers aided by computer algorithms to identify cancer and predict outcomes;
2. Biological markers circulating in the blood or sputum such as abnormal tumor cells the or molecular presence of suspicious cancer-related proteins;
3. Immunotherapy (IO) including various combinations with chemotherapy in first and second and consolidation;
4. Adjuvant-targeted and IO-improving DFS;
5. BBB penetration ability of Alectinib and Tagrisso (Osimertinib) to treat NSCLC brain metastases;
6. Uncovering resistance mechanisms to TKI and investigations researching adjustments to treatment protocols,
7. Using sensitive technology to analyse circulating tumorous DNA.

Dr. Abed Agbarya
Dr. Elizabeth Dudnik
Dr. Maximilian J. Hochmair
Guest Editors

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• non-small-cell lung cancer
• immunotherapy
• molecular genetics and proteomics profiling
• mutation-targeted anticancer drug
• tumor drug resistance
• new therapeutic molecules
• individualized tailored medicine
• biological markers in blood or sputum
• chemotherapy
• early detection