Chemotherapy

Dr. Pitroda and his team will develop a biomarker signature that can predict which patients are the most likely to benefit from an immunotherapy-radiation therapy combination. The ultimate goal is to determine which patients are likely to benefit from this combination treatment.

Checkpoint inhibitors, a type of immunotherapy, are now available in the first-line and second-line settings for certain subsets of NSCLC patients. Furthermore, the U.S. Food and Drug Administration recently approved an immunotherapy-combination treatment regimen for the treatment of a subset of advanced-stage NSCLC patients. While we are making progress in combining and sequencing immunotherapy with other conventional treatments, it is still unclear which patients will respond to these combinations. Dr. Kellie Smith’s laboratory is studying immune cells in blood samples from patients who have received the recently approved combination therapy. She postulates that immune cells from patients receiving the combination behave very differently from immune cells from patients who have received single-agent immunotherapy. Dr. Smith’s team will identify and exploit these differences to develop a blood test that will help predict which patients may benefit from combination therapies, thereby sparing patients the exposure to ineffective treatments.

Surgery is often recommended for patients who have localized lung cancer. Dr. Bogolioubov is analyzing how fast lung cancer comes back after surgery to remove the primary tumor. He is also evaluating the role of chest CT radiography for post-operative follow-up.

Cancer cells develop resistance to chemotherapy drugs by 1) making proteins that neutralize the effects of chemotherapy (through a protein called Bcl-2) and 2) developing pumping systems that expel the drugs out of the cells (through a protein called MRP). Dr. Minko is studying how stopping the Bcl2 and MRP proteins will make lung cancer cells more sensitive to chemotherapy drugs.

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. 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. 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.

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.

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.