Epidermal growth factor receptor (EGFR)

Bexarotene is a synthetic form of retinoid acid (Vitamin A) that has the potential for use in lung cancer chemoprevention. Dr. Petty is conducting a clinical trial with a treatment combination of bexarotene and erlotinib (Tarceva) in EGFR-positive patients who have metastatic non-small cell lung cancer (NSCLC). He is also evaluating biomarkers that will predict response to the combination regimen.

Dr. Pao’s research may determine whether specific mutations in tyrosine kinase genes make lung tumors vulnerable to EGFR-TKIs. A comprehensive analysis of the tyrosine kinase in lung cancers could also lead to new opportunities for drug development and more personalized molecularly targeted therapies.

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.

EGFR tyrosine kinase inhibitors (TKIs) are the mainstay for treatment for non-small cell lung cancer (NSCLC) patients whose tumors have mutations in the EGFR gene. Unfortunately, cancer cells eventually become resistant to TKIs. Dr. Krysan's laboratory has discovered that NSCLC cells produce a chemical called PGE2 that helps lung cancer cells grow in the presence of EGFR TKIs. This suggests that PGE2 helps cancer cells develop acquired resistance to TKIs. Dr. Krysan’s current research is to determine how PGE2 works.

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.

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.

Targeted therapies have shown great promise. However, up to 40% of patients with lung cancer do not test positive for a known target. Dr. Rebecca Heist is studying this group of patients and using DNA sequencing technology to identify novel targets for treatment.