Funded Projects

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.

Dr. Neamati is carrying out in-depth preclinical studies on a prototype compound, SC21. He is studying where the SC21 compound travels in the body, its safety, and its effectiveness in non-small cell lung cancer (NSCLC), with the ultimate goal of bringing SC21 to the clinic.

Heat shock proteins (HSPs) are a class of proteins that are central to the survival of cells, in particular those under stress. Inhibiting HSPs makes cells very sensitive to cell death under stressed conditions (e.g., during chemotherapy). Dr. Salgia is studying the role of HSP27 in lung cancer to develop targeted therapies that are effective against it.

Fibroblasts are cells found in different tissues of the body, including lung tissue. Dr. Arenberg is studying differences in the types of proteins made by tumor-derived lung fibroblast cells and by normal lung fibroblast cells. With an understanding of which proteins make a tumor-derived fibroblast behave in such a way as to promote tumor growth and spread, there is potential to therapeutically target them.

Transcription factors are specialized proteins that translate the DNA footprint of cells to make RNA, which eventually helps to make proteins. Dr. Blancafort plans to use artificial transcription factors (ATFs) to identify and regulate genes involved in lung cancer disease progression. This research will lead to the identification of new markers of progression that could be used as early predictors of lung cancer.

Dr. Dang is studying the anti-tumor effect of gamma-secretases inhibitors, compounds that inhibit activation of the Notch pathway that is active in lung cancer cells. She is studying its effect both alone and in combination with traditional chemotherapy and targeted therapy.

Dr. González Santamaria is investigating how the degradation of certain tumor suppressors (genes that stop cancer development) is accelerated and how that of certain onco-proteins (proteins that cause cancer) is slowed down in lung tumors. Her research will provide a platform for predicting the outcome for lung cancer patients.

Dr. Haura’s hypothesis is that the tyrosine kinase SRC and the protein Stat3 are ideal targets for cancer therapy in lifelong non-smokers who develop lung cancer resulting from EGFR mutations. He is conducting experiments to demonstrate that inhibitors of SRC and/or Stat3 can kill cancer cells. Such inhibitors may have additive effect when used in connection with EGFR inhibitors such as gefitinib or erlotinib.

Dr. Meyerson is exploring how a mutation in the EGFR cells can lead to cancer as well as what the mechanisms are for acquired resistance to EGFR therapies.

Dr. Powell is identifying and characterizing molecular changes that are important in lung adenocarcinoma differentiation (changes in cancer cell shape and size) and invasiveness (ability to spread to other parts of the body). His long-term goal is to use these biomarkers to facilitate early diagnosis, refine prognostic assessment, and develop new therapeutic targets for lung cancer treatment and prevention.

By modeling acquired resistance to gefitinib and erlotinib in the laboratory using a non-small cell lung cancer (NSCLC) cell line that is sensitive to these drugs, Dr. Sharma hopes to uncover the molecular basis for acquired resistance of NSCLC to these targeted therapeutics as well as clues to overcoming this resistance.