The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

An update on the progress of the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) consortium is being presented during the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain. 

The INTEGRAL consortium was designed to be complementary to other initiatives aimed at identifying individuals at high risk for lung cancer, such as radiographic screening programs, in that its objectives involve uncovering predictors of smoking and lung cancer.  

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The 3 projects being undertaken as part of this initiative are focused on:

  1. Gaining an enhanced understanding of genetic factors influencing smoking behavior and the risk of lung cancer
  2. Identifying and validating biomarkers for individuals at high risk of developing lung cancer
  3. Investigating cohorts of patients undergoing radiographic screening for lung cancer to determine the association of specific patient-related factors/biomarkers with the development and behavior of lung cancer

As part of project 1, genome-wide association studies are being performed to identify genomic variants that influence lung cancer risk through modifications of signaling pathways or through environmental interactions.

A study involving multiple cohorts of different ethnicities identified specific interactions between the human leukocyte antigen (HLA) system and tumor peptides as central to the modulation of lung cancer risk. Furthermore, different HLA gene alleles were found to be associated with these interactions when European and Asian cohorts were evaluated separately. Novel biomarkers of lung cancer risk identified in project 1 may be further studied in project 2.

Interestingly, “this effort found a surprising result: that elevated levels of vitamin B12 increase[d] risk for lung cancer development,” the study authors wrote in the abstract.

Regarding the identification of biomarkers in project 2, a panel of 4 circulating proteins – cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), and precursor form of surfactant protein B (Pro-SFTPB) – was shown to have an accuracy of 83% in predicting risk of a lung cancer diagnosis. This risk prediction model is being considered as a tool for identifying patients for enrollment in clinical studies involving radiographic screening for lung cancer.

Project 3 is being conducted in conjunction with low-dose CT (LDCT) screening programs of patients at high risk of lung cancer. It involves the extraction of radiologic features for radiomics analyses, and the creation of models to assess risk of lung cancer associated with noncalcified pulmonary nodules that are detected by LDCT. As mentioned in the context of project 2, researchers are planning to incorporate validated biomarkers of lung cancer risk into lung cancer screening.

These 3 complementary projects involve the use of shared data and samples, and the initiative “draws on world-wide resources and expertise.”

It is anticipated that the integrated findings from these 3 projects will elucidate molecular mechanisms of lung cancer development and facilitate the identification of individuals who would be most likely to benefit from CT screening for lung cancer. 

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

Reference

Amos CI, Huang RJ, Brennan P, et al. The U19 plans for integration of biomarkers into future lung cancer screening. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract S01.07.