Targeted therapy

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.

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.

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.

Dr. Baldwin is identifying and testing new therapeutic targets for KRAS-positive lung cancer. KRAS activates the factor NF-κβ, which, when abnormally active, can contribute to the growth of lung tumors. This activation involves two kinases, and well-validated inhibitors of these pathways exist. This project is determining whether these inhibitors will block the initiation and/or progression of lung tumors.

The IDO protein stops immune cells from recognizing cancer cells and mounting an attack against the cancer. Dr. Prendergast is determining how the IDO protein works in non-small cell lung cancer cells that have mutations in the KRAS gene. He is also testing new compounds that can inhibit IDO in non-small cell lung cancer.

Genes that can suppress the development of tumors are often lost or silenced during the development of human lung tumors. Because they function as a “brake” that normally prevents the onset of lung tumors, they provide new targets for the development of replacement therapies for the effective treatment of lung cancers. Dr. Lisanti is testing the effectiveness of the replacement of a novel tumor suppressor gene, caveolin-1.