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Assessing the Current State of Lung Cancer Chemoprevention: A Comprehensive Overview.

ABSTRACT: Chemoprevention of lung cancer is thought to significantly reduce the risk of acquiring these conditions in the subpopulation of patients with underlying health issues, such as chronic obstructive pulmonary disorder and smoking-associated lung problems. Many strategies have been tested in the previous decades, with very few translating to successful clinical trials in specific subpopulations of patients. In this review, we analyze these strategies, as well as new approaches that have emerged throughout the last few years, including synthetic lethality concept and microbiome-induced regulation of lung carcinogenesis. Overall, the continuous effort in the area of lung chemoprevention is required to develop practical therapeutical approaches. Given the inconsistency of results obtained in clinical trials targeting lung cancer chemoprevention in various subgroups of patients that differ in the underlying health condition, race, and gender, we believe that individualized approaches will have more promise than generalized treatments.

SUBMITTER: Ashraf-Uz-Zaman M

PROVIDER: S-EPMC7281533 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Assessing the Current State of Lung Cancer Chemoprevention: A Comprehensive Overview.

Ashraf-Uz-Zaman Md M Bhalerao Aditya A Mikelis Constantinos M CM Cucullo Luca L German Nadezhda A NA

Cancers 20200517 5

Chemoprevention of lung cancer is thought to significantly reduce the risk of acquiring these conditions in the subpopulation of patients with underlying health issues, such as chronic obstructive pulmonary disorder and smoking-associated lung problems. Many strategies have been tested in the previous decades, with very few translating to successful clinical trials in specific subpopulations of patients. In this review, we analyze these strategies, as well as new approaches that have emerged thr ...[more]

PMID: 32429547

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Project description:Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%. Recently, immunotherapy with checkpoint inhibitor agents have demonstrated responses in advanced NSCLC, with some patients exhibiting durable responses after discontinuing therapy. In 2015, two immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), nivolumab and pembrolizumab were approved for second-line therapy of NSCLC. In 2016, another checkpoint inhibitor targeting program death-ligand 1 (PD-L1), atezolizumab was approved for the same indication. Moreover, pembrolizumab also received approval in 2016 for first-line NSCLC treatment in patients with high PD-L1 expressing tumors. Immunotherapy for NSCLC has therefore, recently evolved into a true treatment modality with the acceptance of PD-1 and PD-L1 inhibitors as the new standard of care for second-line treatment. However, it is still at the discretion of the treating physician whether to use PD-1 or PD-L1 inhibitor as data to compare these two pathways is lacking. Focus is now also on exploring their role in the adjuvant and consolidation settings for NSCLC as well as on exploring novel combinations combining these agents with chemotherapy or radiation. Research is also needed in the development of predictive and prognostic biomarkers for these agents. While vaccine therapy trials in NSCLC have so far failed to show significant clinical benefit, the demonstration of enhanced immune response in these trials suggest the vaccine therapy needs additional evaluation in combination with other therapeutic modalities especially checkpoint inhibition.

Dataset Information

Assessing the Current State of Lung Cancer Chemoprevention: A Comprehensive Overview.

Publications

Assessing the Current State of Lung Cancer Chemoprevention: A Comprehensive Overview.

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