Targeted therapy

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.

Patients with EGFR mutations are treated with EGFR drugs such as gefitinib (Iressa) and erlotinib (Tarceva). However, the cancer cells eventually develop resistance to these drugs. Dr. Sharma is  aiming to understand the processes by which non-small cell lung cancer cells develop resistance to gefitinib and erlotinib as well as  how these processes can be targeted to develop new therapeutic strategies for patients in whom gefitinib and erlotinib have failed.

Cancer-causing proteins called heat shock proteins (HSPs) protect cancer cells from the effects of chemotherapy. Dr. Regan is testing how inhibiting the protein chaperon HSP90 affects the growth of different lung cancer cells.

The p53 gene can stop cells from becoming cancerous. It is mutated in non-small cell lung cancer, allowing cancer cells to grow in an uncontrolled manner. Dr. Duan is evaluating whether a new type of targeted therapy called PRIMA-1, used alone or in combination with other chemotherapies such as cisplatin, can stop the growth of non-small cell lung cancer cells.

Dr. Adusumilli is studying patients who underwent surgery for early-stage lung cancer but whose lung cancer returned because of a condition in which the cancer extends to the pleural membrane covering the lung cancer. Using genetic engineering, Dr. Adusumilli is modifying the patient’s own immune cells in a way that may not only eliminate the spread of tumor cells to the pleura but may also treat the spread of the cancer by tumors too small to be detected.

The rationale behind Dr. Goodglick’s research is that the hormone estrogen and estrogen-pathway activation are important for lung cancer progression. Aromatase is an enzyme that makes estrogen in the body. Dr. Goodglick is conducting extensive pre-clinical evaluations of three aromatase inhibitors to understand steps in the estrogen stimulation pathway that affect tumor progression.