Therapeutics Award

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.

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. Cote is examining the role of estrogen-related tumor characteristics in predicting differences in survival between men and women after a lung cancer diagnosis. The identification of molecular and genetic profiles associated with survival will help target treatment advances and customize treatment for male and female lung cancer patients.

Dr. Klinge is studying why there is a gender bias in lung adenocarcinoma that results in women being at higher risk for developing it. Her studies have revealed which proteins are expressed differently by gender in lung adenocarcinoma cells and how they could be targets of therapy in lung adenocarcinoma.

In order to identify mutated genes that cause lung cancer, Dr. Starr has developed a system that is capable of randomly mutating genes within cells, resulting in tumor formation. The genes mutated by this method can easily be identified using standard molecular biology techniques. He can then test their role in lung cancer formation. 

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.

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.