Molecular profile or molecular testing

Hedgehog signaling

Targeted therapy

Read more about Uncovering Molecular Markers of Hedgehog Antagonist Sensitive Lung Cancer

Heterogeneity of Microarray-based Lung Cancer Signature in Patients with Lung Cancer

2008

Funded by LUNGevity Foundation and The CHEST Foundation

Scott L. Shofer, MD

Durham VA Medical Center Pulmonary Service

Durham

Dr. Shofer’s research builds on work of earlier investigators who developed a lung cancer risk signature based on genetic changes in lung cells in smokers. Dr. Shofer hypothesizes that the lung cancer risk signature model is an indicator of how lung cells change during the process of cancer development. Should his hypothesis be correct, the lung cancer risk signature could be established as a sensitive biomarker capable of diagnosing patients with lung cancer by checking cells taken from the throat using a swab.

Key words

Mutation profile

Stage I

Read more about Heterogeneity of Microarray-based Lung Cancer Signature in Patients with Lung Cancer

Diagnostic Test Development for Non-Small Cell Lung Cancer: Early Detection of Lung Cancer

2008

Funded by LUNGevity Foundation and Partnership for Cures

Jeffrey A. Borgia, PhD

Rush University Medical Center

Chicago

Dr. Borgia is working to develop new biomarkers to strengthen the capabilities of the existing blood test for identifying the presence of metastatic progress in non-small cell lung cancer that he has developed. He plans to adapt the blood test to a diagnostic card format so that high-risk individuals can put blood droplets on diagnostic cards at home and mail them to a test facility where the blood will be extracted and tested for the biomarkers in the panel.

Key words

Risk profile

Read more about Diagnostic Test Development for Non-Small Cell Lung Cancer: Early Detection of Lung Cancer

A microRNA profile to predict recurrence after surgical resection of stage I non-small cell lung cancer

2009

Funded equally by LUNGevity Foundation and the Thoracic Surgery Foundation

Sai Yendamuri, MD

State University of New York at Buffalo

Buffalo

Dr. Yendamuri is conducting a clinical trial among stage-1 non-small cell lung cancer patients to confirm a microRNA signature for the prediction of the recurrence of lung cancer after surgery. He then will develop a blood-based microRNA profile for the detection of lung cancer recurrence.

Key words

Read more about A microRNA profile to predict recurrence after surgical resection of stage I non-small cell lung cancer

CHFR methylation as novel predictor for chemotherapy response in NSCLC

2009

Funded equally by LUNGevity Foundation and The CHEST Foundation

Johann C. Brandes, MD, PhD

Emory University

Atlanta

The CHFR gene is a gene that has undergone changes in its DNA. Dr. Brandes is studying how the CHFR gene predicts a non-small cell lung cancer patient’s response to chemotherapy.

Key words

Chemotherapy

Metastatic

Read more about CHFR methylation as novel predictor for chemotherapy response in NSCLC

DNA Methylation Changes in Peripheral Blood Mononuclear Cells as Biomarkers of Lung Cancer

2009

LUNGevity Foundation/Uniting Against Lung Cancer Research Grant

William P. Bennett, MD

Beckman Research Institute at the City of Hope

Duarte

Dr. Bennett is evaluating potential biomarkers for their use in identifying lung cancer patients by comparing blood samples taken from patients with lung cancer and from patients without lung cancer. His goal is to build a panel of biomarkers that will aid in diagnosis.

Key words

Read more about DNA Methylation Changes in Peripheral Blood Mononuclear Cells as Biomarkers of Lung Cancer

Molecular signatures to predict response in neoadjuvant chemoradiation therapy of Stage III NSCLC patients

2009

LUNGevity Foundation/Respiratory Health Association of Chicago Research Grant

Jeffrey A. Borgia, PhD

Rush University Medical Center

Chicago

Dr. Borgia is developing a process based on biomarkers derived from tissue and clinical factors such as age, smoking history, histology, and stage of diagnosis of lung cancer. This process will identify which patients with advanced-stage lung cancer will respond to medical treatment and thus qualify for surgery that potentially could cure the cancer.

Key words

Chemotherapy

Mutation profile

Squamous cell lung cancer

Radiotherapy

Stage III

Read more about Molecular signatures to predict response in neoadjuvant chemoradiation therapy of Stage III NSCLC patients

Developing Novel Biomarkers and Targets to Address Small Cell Lung Cancer

2009

LUNGevity Foundation/The University of Kansas Cancer Center Research Grant

Sitta Sittampalam, PhD

University of Kansas Medical Center

Kansas City

Chao Huang, MD

Dr. Sittampalam is determining whether circulating tumor cells can be a useful blood-based tumor marker in untreated patients with extensive-stage small cell lung cancer who are planning to receive chemotherapy. He is also exploring the feasibility of genomic profiling using circulating tumor cells.

Key words

Circulating tumor cells

Small cell lung cancer (SCLC)

Mutation profile

Read more about Developing Novel Biomarkers and Targets to Address Small Cell Lung Cancer

MiRNA expression profiling to predict recurrence after resection of stage I NSCLC

2009

National Lung Cancer Partnership/LUNGevity Foundation Research Grant

Sai Yendamuri, MD

State University of New York at Buffalo

Buffalo

Key words

Stage I

Read more about MiRNA expression profiling to predict recurrence after resection of stage I NSCLC

Combined Protein and miRNA Profiles for the Early Detection of Lung Cancer

2010

Protect Your Lungs/ LUNGevity Foundation Research Grant; funded in part by A Breath of Hope Foundation

Steven M. Dubinett, MD

David Geffen School of Medicine at UCLA

Los Angeles

Krysan Kostyantyn, PhD

David Geffen School of Medicine at UCLA

Los Angeles

Lung cancer cells produce different types of proteins and RNA molecules that circulate in the blood. Dr. Steven Dubinett and his team have discovered 17 unique miRNAs in the blood of lung cancer patients and other high-risk individuals, such as smokers. Blood of healthy and low-risk people do not have these miRNAs. They are developing an miRNA-based blood test to predict which high-risk individual might develop lung cancer.

Research Summary

Lung cancer accounts for more than 28 percent of all cancer deaths each year and is the leading cause of cancer related mortality in the United States causing more deaths than prostate, colon and breast cancers combined Despite focused research in conventional therapies, the five-year survival rate remains only 15 percent. Due to anti-tobacco initiatives the number of active smokers in the US is steadily declining, however recent studies suggest that individuals who quit smoking continue to have an elevated risk of lung cancer that may not return to baseline risk for as much as 30 years following smoking cessation. Owing to the lack of reliable early diagnostic techniques, most patients are being diagnosed with advanced stage disease that his inoperable and therefore they have a poor prognosis. Thus, there are more than 100 million current and former smokers in the US who have elevated risk for lung cancer and may benefit from a non-invasive test for early detection.

Patients at risk for lung cancer may have undetected disease for years prior to diagnosis. The clinical challenge is therefore to develop lung cancer detection methods that are effective during this window of opportunity to increase the rate of early detection and thereby spur early treatment and improve lung cancer patient outcomes. During tumorigenesis, the developing tumor forms a microenvironment that is comprised of many components and cell types. These complex cellular populations produce many soluble factors that could be important for tumor initiation and growth and thus potentially serve as lung cancer biomarkers. Small tumors, initiated in this environment, may remain undetected; however, the profile of soluble factors produced by the tumor mircorenvironment will be altered in the peripheral blood of cancer patients and could therefore have utility for the development of a diagnostic panel for early lung cancer detection. Because the blood vessels in the lungs comprise approximately 50% of the body’s total vasculature, the peripheral blood is expected to serve as a non-invasive biospecimen that reflects even small variations in lung cancer biomarkers. We hypothesize that interactions between tumor cells and host cells recruited into the local tumor microenvironment will result in the production of a unique biomarker signature composed of proteins and microRNA (miRNA) important for cancer progression.

Over the past decade, our laboratory has gathered substantial data supporting the analysis of soluble mediators of lung carcinogenesis including inflammatory, growth and angiogenic factors and miRNA. Additionally, since our early investigations, a considerable literature has developed describing the contribution of these factors to lung carcinogenesis. Based on these findings, in our preliminary studies we have developed a plasma protein-based biomarker panel that accurately distinguishes smokers with and without lung cancer. Our predictive model provided 97% sensitivity.

Technical Abstract

Despite focused research in conventional therapies, the 5-year survival rate of lung cancer patients remains only 15%. Due to the lack of reliable early diagnostic techniques, most patients are diagnosed with advanced-stage disease and therefore have a poor prognosis. There are more than 100 million current and former smokers in the US who have elevated risk for lung cancer and may benefit from a non-invasive test for early detection. Patients at risk may have subclinical disease for years prior to diagnosis. Therefore the clinical challenge is to develop lung cancer detection methods that are effective during this window of opportunity to increase the rate of early detection and thereby spur early treatment and improve lung cancer patient outcomes. During tumorigenesis, the developing tumor forms a complex cellular microenvironment that produces many soluble mediators, such as proteins and miRNAs, which are important for tumor initiation and growth and thus can serve as lung cancer biomarkers. Because the pulmonary vascular bed comprises approximately 50% of the body’s total vasculature, the peripheral blood is expected to reflect even small variations in lung cancer biomarkers.

Over the past decade, our laboratory has gathered substantial data supporting the analysis of soluble mediators of lung carcinogenesis including inflammatory cytokines, growth and angiogenic factors, and miRNA. Additionally, a considerable literature has developed describing the contribution of these factors to lung carcinogenesis. Based on these findings, in our preliminary studies we have developed a plasma protein-based biomarker panel that accurately distinguished between lung cancer patients and at-risk control subjects. Our predictive model provided 97% sensitivity, 77% specificity, and an area under the ROC of .93 for stage 1 vs. high-risk controls. Because recent studies demonstrated that circulating miRNA can serve as robust and specific diagnostic biomarkers, we developed a panel of 17 miRNAs relevant to lung carcinogenesis. In our preliminary studies utilizing this miRNA panel, we were able to detect miRNAs that are differentially expressed in the plasma of lung cancer patients as compared to high-risk controls. We hypothesize that the proteins and miRNA profiles will each contribute unique information and thus, an integrated panel of protein and miRNA markers may provide higher sensitivity for early lung cancer detection than either platform alone.

Specific aims for the current proposal include: 1) to identify protein profiles in plasma associated with early-stage lung cancer, 2) to identify plasma miRNA profiles associated with early stage lung cancer, and 3) to integrate miRNA and cytokine biomarkers established in Aims 1 and 2 to improve early-stage lung cancer detection. The first and second aims address the clinical problems of patients at risk for lung cancer who present with a suspicious pulmonary nodule of indeterminate significance that has be further evaluated.

Key words