Targeted therapy

Agents that activate the PPARgamma protein have already been used  in the treatment of diabetes and atherosclerosis. Dr. Keshamouni is researching whether and how they affect the growth of non-small cell lung cancer (NSCLC) cells.

Dr. Pao’s research may determine whether specific mutations in tyrosine kinase genes make lung tumors vulnerable to EGFR-TKIs. A comprehensive analysis of the tyrosine kinase in lung cancers could also lead to new opportunities for drug development and more personalized molecularly targeted therapies.

Angiogenesis is the process by which cancer cells recruit blood vessels to the tumor. This aids the growth of cancer cells by providing nutrition and oxygen to them. Dr. Vlahakis is studying how a protein called VEGF-A interacts with certain proteins expressed on the surface of lung cells to control the angiogenesis process.

Dr. Ma has identified mutations in the protein c-Met that may provide lung tumor cells the ability to metastasize. Dr. Ma is studying the role of c-Met and its genetic alterations in lung adenocarcinoma to better understand their functional implications.

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.

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.

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. 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.

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.

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.