Non-small cell lung cancer (NSCLC)

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.

NNK is a powerful nicotine-derived carcinogen. Dr. Schuller is determining the exact role of estrogen in tumors caused by NNK. This understanding will provide new targets for the early diagnosis, prevention, and therapy of lung cancer in women.

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.

Dr. Tainsky has developed a technology that takes advantage of the responses of the human immune system to identify cancer-associated proteins that bind to antibodies present in the blood of cancer patients but not in the blood of healthy subjects or those with benign diseases. Dr. Tainsky is working to develop a non-invasive screening test for the early detection of lung cancer by using cancer-associated antigens as biomarkers.

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.

When cancer cells start spreading to other parts of the body, their shape changes through a process called EMT (epithelial-to-mesenchymal transition). The process of EMT in non-small cell lung cancer cells is mediated by the Snail protein. Dr. Yanagawa is studying how the Snail protein controls the EMT process through a protein called MMP2.

Previously conducted clinical trials have suggested an increased risk of lung cancer from hormone replacement therapy (HRT). Dr. Slatore is studying women who have both undergone HRT and smoked  to determine whether there is a relationship between HRT, tobacco use, and lung cancer.