Lung Cancer: Recovery Act Investment Report

November 2009

Public Health Burden

Lung cancer is the leading cause of cancer-related death among both men and women in the United States, with nearly 160,000 people expected to die of the disease in 2009. Reductions in tobacco use—the major cause of lung cancer—have led to the recent decline in the incidence of this disease among men and the plateauing of incidence among women following long periods of increase. Nevertheless, about 220,000 people will be diagnosed with lung cancer in 2009. Since 1987, more women have died each year from lung cancer than from breast cancer.

Prevention

Smoking cessation and avoiding exposure to tobacco smoke are effective ways of reducing the risk of lung cancer. However, researchers are also exploring the possibility of using pharmacologic agents to block or reverse the progression of premalignant lung lesions to malignant tumors. Several different ARRA-funded research projects are focused on lung cancer prevention, including the following:

• Investigating how the use of tobacco and alcohol by adolescents and young adults may be related to exposure to images in movies, television, and industry marketing and advertising campaigns, and determining whether these exposures should be reduced.(1)
• Evaluating three agents (bexarotene, vorinostat, and sulindac) that may inhibit lung cancer development and progression to compare the effectiveness of single versus combined administration and concurrent versus sequential administration in a mouse model of lung cancer.(2)

Detection/Diagnosis

Because most lung cancers are not diagnosed until the disease is advanced, early detection and diagnosis are critical to improving lung cancer outcomes. Although several early detection methods have been studied—including chest X-ray, spiral computed tomography (spiral CT), and sputum cytology (looking for abnormal cells in sputum)—none has yet been shown to help reduce lung cancer deaths, and it is not clear that the benefits of these techniques outweigh the risks. The identification of molecular markers of disease risk, tumor classification at diagnosis, and prediction of response to treatment are promising areas of investigation. ARRA funding is supporting research in these areas, including:

• A study to test the validity of a lung cancer risk test in which the status of 14 genes in airway epithelial cells obtained by bronchoscopy is examined; in addition airway epithelial cells and blood samples from study participants will be archived for biomarker analysis; the results of this study could help identify individuals most likely to benefit from screening and prevention interventions.(3)
• A study that will use a novel phosphoproteomics platform to profile the global state of tyrosine phosphorylation in non-small cell lung carcinoma (NSCLC); the goal is to determine whether this information can be used to classify NSCLC tumors, predict their behavior, and guide treatment with tyrosine kinase inhibitors and/or other therapies.(4)

Treatment

For most patients with lung cancer, the results of treatment with existing therapies are poor except for patients with highly localized disease. Although some current treatments can lead to prolonged disease remission, the 5-year survival rate for all stages of lung cancer combined is approximately 16 percent. Therefore, improving treatment of this disease is a high priority. ARRA-funded research is investigating several approaches to improving lung cancer therapy, including the following:

• Several lung cancer clinical trials being conducted under NCI's Accelerating Clinical Trials of Novel Oncologic Pathways (ACTNOW) program are receiving ARRA support, including a phase II trial in which patients with advanced small-cell lung cancer will be treated with chemotherapy plus one of two new therapies that target molecules involved in cancer cell growth or survival, a phase I trial in which patients with brain metastases from non-small cell lung cancer will be treated with an inhibitor of tumor blood vessel formation in combination with whole brain radiation therapy, and a phase II trial in which two different imaging techniques will be used to monitor pre-surgical response to chemotherapy in patients with operable non-small cell lung cancer; the goal of ACTNOW is to shorten the time it takes to move new cancer treatments from the discovery phase, to development, and, ultimately, to approval and safe use by cancer patients.(5, 6, 7)
• A project to improve the accuracy and reliability of cone-beam computed tomography guidance of radiation treatment by reducing the blur and distortion caused by the motion of breathing; the effectiveness of the developed approach will be tested in patients with lung cancer or liver metastases who are undergoing radiation treatment.(8)

Genomic Research

Genomic changes caused by carcinogens in tobacco smoke underlie the development of most lung cancers. Inherited genetic alterations have also been found to affect smoking-related lung cancer risk. Therefore, comprehensive identification of the genomic changes that lead to lung cancer and its progression will advance our understanding of the molecular basis of this disease and improve our ability to diagnose, treat, and prevent it. ARRA funding is supporting lung cancer-related genomic research in several areas, including the following:

• Squamous cell lung carcinoma, a type of non-small cell lung cancer, has been added to the cancers being studied in The Cancer Genome Atlas (TCGA) project, a collaborative effort involving NCI and the National Human Genome Research Institute (NHGRI).
• A genome-wide screen will analyze the DNA of 1200 lung cancer patients and 1200 control subjects to identify genetic regions associated with the development of lung cancer; one goal is to improve our understanding of how genes interact with other genes and with the environment in lung cancer development.(9)

Selected References

1.  3R01CA077026-12S1 — Visual media influences on adolescent smoking behavior  — Sargent, James D. (NH)
2.  1R21CA135335-01A1 — Prevention of lung tumors by agents using concurrent and sequential treatment — Pereira, Michael A. (OH)
3.  1RC2CA148572-01­— Validation of a multi-gene test for lung cancer prediction — Willey, James C. (OH)
4.  1RC1CA146843-01 — A novel molecular diagnostic approach to classify lung cancers and predict response — Mayer, Bruce J. (CT)
5.  U10 CA 21115 — A Randomized Phase II Study of Cisplatin and Etoposide in Combination with Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for Patients with Extensive Stage Small Cell Lung Cancer — Comis, Robert L. (MA)
6.  U01 CA 62490 — A Phase I Study of AZD2171 and WBRT in Patients with Brain Metastases from Non-Small Cell Lung Cancer — Kufe, Donald W. (MA)
7.  N01 CM 27018  — Phase II Single-Arm Trial Comparing the Use of FLT PET to Standard Computed Tomography to Assess the Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable Non-Small Cell Lung Cancer — Macura, Katrzyna (MD)
8.  3R01CA126993-02S1 ­— Respiratory motion-reduced cone-beam CT guidance of radiotherapy in lung and liver — Mageras, Gikas S. (NY)
9.  3R01CA121197-03S1 — High-density association analysis of lung cancer — Amos, Christopher I. (TX)