Understanding Non-small Cell Lung Cancer: Biology, Therapeutics and Drug Resistance

Dear Colleagues,

Lung cancer is one of the primary causes of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Unfortunately, the 5-year survival rate for regional and distant NSCLCs remains poor at 37% and 9%, respectively. Treatment approaches such as radiation therapy, endocrine therapy, chemotherapy and targeted therapies, particularly those targeting EGFR (such as erlotinib or gefitinib) have shown substantial clinical benefits. Recent advancements in molecular profiling, such as identifying specific alterations in genes, e.g., ALK, RET, ROS1, EGFR, KRAS and BRAF, among others through emerging technologies such as next-generation sequencing (NGS), have aided clinicians in identifying appropriate treatment regimens. In the last decade, immunotherapeutic drugs such as anti-PD-1 (Nivolumab, Pembrolizumab) and anti-PD-L1 (Atezolizumab) have been introduced for the treatment of advanced NSCLC. While these therapies have significantly improved the survival rates of cancer patients, the majority of patients still do not benefit from these modalities. One significant challenge in treating NSCLC is the development of drug resistance, which impedes efforts to control the spread and recurrence in cancer patients. The majority of patients experience acquired resistance to chemotherapy or immunotherapy within a few years of treatment initiation. Thus, there is a continued need to identify molecular mechanisms underlying drug resistance and pursue the development of new therapeutic strategies. Additionally, novel prognostic and predictive biomarkers are required to accurately stratify cancer patients. Through the definition of the molecular underpinnings of drug resistance and associated biomarkers, using personalized treatment approaches can improve patient outcomes, thus mitigating the morbidity and mortality of lung cancer.

      This Special Issue will seek contributions of research articles and reviews covering a broad spectrum of NSCLC studies, including, but not limited to:

1. NSCLC biology: the characterization of novel driver mutations, molecular mediators of transformation and metastasis, metabolic reprogramming and the role of stromal elements within the tumor microenvironment;
2. NSCLC biomarkers: the characterization and validation of diagnostic, prognostic and predictive biomarkers;
3. NSCLC classification: new approaches for the classification of tumors through the incorporation of genomics, transcriptomics and proteomics. Incorporation of emerging methodologies from the fields of computational biology, machine learning and/or quantitative modeling;
4. NSCLC therapeutics: novelapproaches to enhance molecular interrogation techniques and promising approaches to overcome resistance using a variety of in silico, in vitro and in vivo models. Advances in research describing chemotherapy, targeted therapy and immunotherapy are also welcome.

Dr. Mumtaz V. Rojiani
Dr. Ravindra Kolhe
Dr. Pankaj Ahluwalia
Guest Editors

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• NSCLC
• therapy
• mutations
• drug resistance
• biomarkers