Targeted therapy

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.

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.

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.

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.

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.

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.