Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a 5-year survival rate of less than 25%. Current treatment modalities include surgery, radiotherapy, and chemotherapy; however, most individuals are diagnosed at a locally advanced or metastatic stage when curative treatments are unavailable. Despite prolonged disease control in response to immunotherapy and tyrosine kinase inhibitors, only a minority of patients derive durable clinical benefit. In some cases, complete responders with minimal to no detectable disease post-treatment eventually succumb to drug-resistance progression. Thus, deeper insights into the immunological and molecular mechanisms that underpin NSCLC drug relapse and therapy resistance are required to improve treatment and survival outcomes.
The goal of this Special Issue is to address current issues and challenges in the diagnosis and treatment of therapy resistant NSCLC.
These include:
- Understanding the molecular, cellular, and pathological factors that underpin resistance mechanisms to therapy, including tumor mutational burden and heterogeneity. We are also interested in understanding the mechanisms that underlie exceptional responses in a small percentage of patients.
- Identification of novel biomarkers to predict resistance to therapy, and the application of these biomarkers to devise rational therapeutic strategies.
- Novel approaches to overcome multi-drug resistance, such as preventing the emergence of resistance or targeting drug-tolerant persistent cells.
- Why tumors evolve on-target vs. off-target resistance mechanisms.
- Development of non-invasive tools to track evolving resistance mechanisms in patients, including liquid biopsy technologies performed in serial longitudinal settings over the course of treatment.
This Special Issue will publish Original Research, Reviews, Perspectives, as well as unique Case Reports. We highly encourage the submission of interdisciplinary and collaborative research.
Sub-topics include but are not limited to:
- Immunological and molecular determinants associated with drug relapse and primary / acquired drug resistance. These may include activation of oncogenic pathways, alternative splicing, gene amplification, resistance mutations, inefficient drug delivery, metabolic inactivation, or influence of the tumor microenvironment.
- Identification of predictive biomarkers associated with early adaptive drug resistance.
- New and emerging technologies, including single-cell methods, sequential liquid biopsy, and multi-region sequencing to identify heterogenous and evolving resistance mechanisms in patients.
- Updates on current protocols and management of patients with progressive disease.
- Strategies for personalized medicine based on oncogenic driver mutations, including combination therapies that target specific resistance pathways.
- Development of pre-clinical models to evaluate drug sensitivity and therapeutic resistance.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a 5-year survival rate of less than 25%. Current treatment modalities include surgery, radiotherapy, and chemotherapy; however, most individuals are diagnosed at a locally advanced or metastatic stage when curative treatments are unavailable. Despite prolonged disease control in response to immunotherapy and tyrosine kinase inhibitors, only a minority of patients derive durable clinical benefit. In some cases, complete responders with minimal to no detectable disease post-treatment eventually succumb to drug-resistance progression. Thus, deeper insights into the immunological and molecular mechanisms that underpin NSCLC drug relapse and therapy resistance are required to improve treatment and survival outcomes.
The goal of this Special Issue is to address current issues and challenges in the diagnosis and treatment of therapy resistant NSCLC.
These include:
- Understanding the molecular, cellular, and pathological factors that underpin resistance mechanisms to therapy, including tumor mutational burden and heterogeneity. We are also interested in understanding the mechanisms that underlie exceptional responses in a small percentage of patients.
- Identification of novel biomarkers to predict resistance to therapy, and the application of these biomarkers to devise rational therapeutic strategies.
- Novel approaches to overcome multi-drug resistance, such as preventing the emergence of resistance or targeting drug-tolerant persistent cells.
- Why tumors evolve on-target vs. off-target resistance mechanisms.
- Development of non-invasive tools to track evolving resistance mechanisms in patients, including liquid biopsy technologies performed in serial longitudinal settings over the course of treatment.
This Special Issue will publish Original Research, Reviews, Perspectives, as well as unique Case Reports. We highly encourage the submission of interdisciplinary and collaborative research.
Sub-topics include but are not limited to:
- Immunological and molecular determinants associated with drug relapse and primary / acquired drug resistance. These may include activation of oncogenic pathways, alternative splicing, gene amplification, resistance mutations, inefficient drug delivery, metabolic inactivation, or influence of the tumor microenvironment.
- Identification of predictive biomarkers associated with early adaptive drug resistance.
- New and emerging technologies, including single-cell methods, sequential liquid biopsy, and multi-region sequencing to identify heterogenous and evolving resistance mechanisms in patients.
- Updates on current protocols and management of patients with progressive disease.
- Strategies for personalized medicine based on oncogenic driver mutations, including combination therapies that target specific resistance pathways.
- Development of pre-clinical models to evaluate drug sensitivity and therapeutic resistance.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
