Funded Projects

Lung cancer screening is not established as a public health practice, yet the results of a large randomized controlled trial among a high-risk population showed that screening with low-dose spiral computed tomography reduces lung cancer mortality. Milliman Consulting Company is conducting a cost-benefit analysis to demonstrate whether improved health outcomes (by catching the lung cancer early so that it can be treated) correlate with increased cost savings among this population.

Dr. Nana-Sinkam is delineating the role of microRNA expression profiling in the diagnosis, management, and prognosis of lung cancer. He is testing whether microRNA expression profiles are detectable in the  blood of lung cancer patients. He will compare individuals with lung cancer with current and former smokers without lung cancer.

Dr. Hastings is establishing how parathyroid hormone-related protein (PTHrP) slows lung cancer growth, evaluating why lung cancers in men are less sensitive to PTHrP, and testing whether changes in hormone levels can affect the growth of lung cancer cells. His research may also determine whether changing the levels of male hormones makes it possible to improve the response to PTHrP.

The role of the hormone estrogen in the development of lung cancer has been established. Dr. Heymach is studying how estrogen affects signaling by the EGFR gene and secretion of proteins that fuel the development of new blood vessels necessary to sustain the growth of the cancer.

Dr. Kim’s hypothesis is that bronchioloalveolar carcinomas, a subtype of non-small cell lung cancer, are maintained by a small population of cells often referred to as cancer stem cells. Dr. Kim is identifying these stem cells and drugs that inhibit them.

The landscape of lung cancer treatment has changed with the initial discovery of an EGFR mutation in 2004. Now, drugs that block specific driver mutations are being considered for the treatment of non-small cell lung cancer (NSCLC). The LOGIC group (Lung Oncology Group in Chicago) is studying the correlative effects of agents used in conjunction with targeted therapies in the treatment of lung cancer.

Two commonly mutated genes in non-small cell lung cancer are KRAS and BRAF. Dr. McDaid is studying how these two genes control the synthesis of proteins in lung cancer cells. She is also testing how targeting the LKB1 mutation that often co-occurs with KRAS mutations can neutralize the effects of the KRAS mutation.

The Hedgehog (Hh) signaling pathway is active in both small cell and non-small cell lung cancer and provides a “don’t stop growing” signal to cancer cells. Dr. Robbins is working to identify and validate a panel of biomarkers that can be used to determine whether the lung cancer is sensitive to drugs that stop Hh signaling.

Dr. Seferos is developing new nanoparticle-based agents that are 13 nanometers in diameter to treat lung cancer. Unlike traditional chemotherapy, these particles can target the cancer cells directly and so reduce the side effects that are commonly associated with chemotherapy.

In order to identify mutated genes that cause lung cancer, Dr. Starr has developed a system that is capable of randomly mutating genes within cells, resulting in tumor formation. The genes mutated by this method can easily be identified using standard molecular biology techniques. He can then test their role in lung cancer formation. 

Human mesenchymal stem cells (MSCs) selectively migrate to tumors of the brain or the lung. MSCs are specialized cells found in the bone marrow. They can form bone, cartilage, fat, and possibly other tissues. Dr. Zielske is researching how to make use of this property of MSCs. He is working on how to deliver locally high concentrations of chemotherapy drugs to the tumor microenvironment while avoiding the side effects associated with chemotherapy, which flows through the bloodstream to most parts of the body.

Dr. Cote is examining the role of estrogen-related tumor characteristics in predicting differences in survival between men and women after a lung cancer diagnosis. The identification of molecular and genetic profiles associated with survival will help target treatment advances and customize treatment for male and female lung cancer patients.

Dr. Fields is generating pre-clinical data to support a clinical trial of a novel compound, autothiomalate (ATM), for the treatment of lung cancer. ATM, which is FDA-approved for rheumatoid arthritis, exhibits anti-cancer activity against non-small cell lung cancer (NSCLC) in preclinical studies.

Dr. Klinge is studying why there is a gender bias in lung adenocarcinoma that results in women being at higher risk for developing it. Her studies have revealed which proteins are expressed differently by gender in lung adenocarcinoma cells and how they could be targets of therapy in lung adenocarcinoma.

EGFR tyrosine kinase inhibitors (TKIs) are the mainstay for treatment for non-small cell lung cancer (NSCLC) patients whose tumors have mutations in the EGFR gene. Unfortunately, cancer cells eventually become resistant to TKIs. Dr. Krysan's laboratory has discovered that NSCLC cells produce a chemical called PGE2 that helps lung cancer cells grow in the presence of EGFR TKIs. This suggests that PGE2 helps cancer cells develop acquired resistance to TKIs. Dr. Krysan’s current research is to determine how PGE2 works.